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Serum Cytokine Induction After a Single Mycobacterium Cell Wall
Fraction (MCWF) treatment in Tumor Bearing Dogs
Martins M Losowski L Masic A Prunic B Rodrigues LCS
WVCC ndash 2016Foz do Iguassu
I Mellman et al Nature 480 480-489 (2011)
Goal of this Study
The aim of this study was to evaluate the ability of MCWF to induce serum cytokine
synthesis after single intravenous treatment in dogs with different solid tumors
Mycobacterium cell wall fraction (MCWF)
Biological Modulator
Induce cytokine production
Induce apoptosis
Filion et al 1999 Morales et al 2015
Human and canine TCC in vitro HT-1376 HT-1197 and K99
Study Design
10 naiumlve dogs with solid tumors
bull Tumor Diagnosis
bull Complete Staging (3 view Chest X-Ray ABD-US)
bull CBC Biochemistry Urinalysis
bull Body Condition Score and ECOG performance Status
MCWF treatment bull 50μgKg in 100mL of 09NaCl over 45min as slow IV infusion
Cytokine Analysis
Study Design
Pre-treatment
bullPE
bullCBC + Biochemistry
bullUrinalysis
bullCytokines
2 hours
bullPE
bullCytokines
4 hours
bullPE
bullCytokines
6 hours
bullPE
bullCytokines
12 hours
bullPE
bullCytokines
24 hours
bullPE
bullCytokines
48 hours
bullPE
bullCBC
bullCytokines
168 hours
bullPE
bullCBC + Biochemistry
bullUrinalysis
bullCytokines
IL-2 IL-6
IL-10 GM-CSF
IFN-γ TNF-α
IL-12
MyBiosourcereg
Milliplexreg MAPCCYTOMAG-90K-06
450nm Luminexreg 200 and Xpontent (Software)
Study Design
Results
Patient ID Breed Sex Age Weight (Kg) BCS
Patient1 Mixed female spayed 17 870 2
Patient2 Mixed female spayed 13 675 4
Patient3 Mixed female spayed 15 470 4
Patient4 Mixed female spayed 10 1460 4
Patient5 Pit Bull Male intact 7 3400 2
Patient6 Labrador Male castrated 10 3010 4
Patient7 Labrador female spayed 15 3290 4
Patient8 Mixed female spayed 12 685 4
Patient9 Mixed Male Intact 13 1800 4
Patient10French Bulldog female spayed 25 970 5
Results
Patient ID Diagnosis Location Clinical Staging Tumor Size
Patient1 Oral Melanoma left mandible V 20 x 23 mm
Patient2 Mammary Tumor right M5 II 32 x 32 mm
Patient3 Mammary Tumor right M5 II 32 x 30mm
Patient4 Mast Cell Tumor left leg Ia 20 x 18mm
Patient5 Osteosarcoma left femur II 85 x 80mm
Patient6 Oral Melanoma right mandible II 50 x 48mm
Patient7 Hepatocellular Carcinoma left lobe I 472 x 297mm
Patient8 Mammary Tumor right M4 II 33 x 29mm
Patient9 Mast Cell Tumor left leg IV 56 x 42mm
Patient10 Mast Cell Tumor inguinal area IV 10 x 7mm
Results
0h 48h 168h
100
200
300
400
500
600
700
Time
Pla
tele
ts (
cell
sm
mˆ3
)
0h 48h 168h0
1
2
3
4
5
6
7
8
9
Time
RB
C (
x10ˆ6
mm
ˆ3)
0h 48h 168h0
5
10
15
20
25
Time
WB
C (
cell
sm
mˆ3
)
- No difference in PE and clinical parameters- Treatment did no change biochemistry
profile- ALT ALP ALB GLOB Tbil TB- CRE BUN PHOS K+ Na+- AMY PHOS GLU Ca
Results
p=00306
Results
IL-10
Inhibitory actions on macrophages and DC
Inhibits the production of IL-12 and IL-2
Decrease the expression of class II MHC
Produced by- T and B Cells- Monocytes- DC- NK
Stimulation of macrophage phagocytosis and NK cytotoxicity
Carson et al 1995
Moore et al 2001 de Waal et al 1993
Inhibitory effects of IL-10 on tumor growth in animal models
Mocelli et al The dual role of IL-10 2003
Co
ntr
ol
IL-1
0
Mocelli et al The dual role of IL-10 2003
J Interferon Cytokine Res 1999 Jul19(7)697-703Regulation of tumor growth and metastasis by interleukin-10 themelanoma experienceHuang S1 Ullrich SE Bar-Eli M
J Exp Med 1996 Aug 1184(2)579-84Interleukin-10 inhibits tumor metastasis through an NK cell-dependent mechanismZheng LM1 Ojcius DM Garaud F Roth C Maxwell E Li Z Rong H Chen J Wang XY Catino JJ King I
Results
Results
Conclusions
bull Single dose of MCWF (50 μgKg) IV increases IL-10 serum levels 2 hours post-treatment with statistically significant difference (p=00306)
bull Dogs treated with MCWF demonstrated significantly improved quality of lifendash appetite activity level playfulness and general health
improvement
bull The clinical effectiveness against various malignancies potential activation of NK and tumor control in dogs with spontaneous tumors are still undetermined
Study Limitations
bull Small number of dogs
bull No healthy dogs as a control
Future Directions
bull Evaluate the biological activity in patients with solid tumors
bull Compare the cytokine production after local treatment
lucasrodriguesestimavetbrACKNOWLEDGMENT
Mirtes MartisLarissa LosowskiDenise SamiaKaique BrazAna Carolina FariaDaiana SousaFelipe FernandesGraziela SantosElena ToazzaElis MontiCarolina FabriLarissa LopesGiza CabralKladine MoniqueSthefany Chagas
Joyce Ana Paula KarenBarbara Michele CharlesAline Andrade - Gisele Paim
I Mellman et al Nature 480 480-489 (2011)
Goal of this Study
The aim of this study was to evaluate the ability of MCWF to induce serum cytokine
synthesis after single intravenous treatment in dogs with different solid tumors
Mycobacterium cell wall fraction (MCWF)
Biological Modulator
Induce cytokine production
Induce apoptosis
Filion et al 1999 Morales et al 2015
Human and canine TCC in vitro HT-1376 HT-1197 and K99
Study Design
10 naiumlve dogs with solid tumors
bull Tumor Diagnosis
bull Complete Staging (3 view Chest X-Ray ABD-US)
bull CBC Biochemistry Urinalysis
bull Body Condition Score and ECOG performance Status
MCWF treatment bull 50μgKg in 100mL of 09NaCl over 45min as slow IV infusion
Cytokine Analysis
Study Design
Pre-treatment
bullPE
bullCBC + Biochemistry
bullUrinalysis
bullCytokines
2 hours
bullPE
bullCytokines
4 hours
bullPE
bullCytokines
6 hours
bullPE
bullCytokines
12 hours
bullPE
bullCytokines
24 hours
bullPE
bullCytokines
48 hours
bullPE
bullCBC
bullCytokines
168 hours
bullPE
bullCBC + Biochemistry
bullUrinalysis
bullCytokines
IL-2 IL-6
IL-10 GM-CSF
IFN-γ TNF-α
IL-12
MyBiosourcereg
Milliplexreg MAPCCYTOMAG-90K-06
450nm Luminexreg 200 and Xpontent (Software)
Study Design
Results
Patient ID Breed Sex Age Weight (Kg) BCS
Patient1 Mixed female spayed 17 870 2
Patient2 Mixed female spayed 13 675 4
Patient3 Mixed female spayed 15 470 4
Patient4 Mixed female spayed 10 1460 4
Patient5 Pit Bull Male intact 7 3400 2
Patient6 Labrador Male castrated 10 3010 4
Patient7 Labrador female spayed 15 3290 4
Patient8 Mixed female spayed 12 685 4
Patient9 Mixed Male Intact 13 1800 4
Patient10French Bulldog female spayed 25 970 5
Results
Patient ID Diagnosis Location Clinical Staging Tumor Size
Patient1 Oral Melanoma left mandible V 20 x 23 mm
Patient2 Mammary Tumor right M5 II 32 x 32 mm
Patient3 Mammary Tumor right M5 II 32 x 30mm
Patient4 Mast Cell Tumor left leg Ia 20 x 18mm
Patient5 Osteosarcoma left femur II 85 x 80mm
Patient6 Oral Melanoma right mandible II 50 x 48mm
Patient7 Hepatocellular Carcinoma left lobe I 472 x 297mm
Patient8 Mammary Tumor right M4 II 33 x 29mm
Patient9 Mast Cell Tumor left leg IV 56 x 42mm
Patient10 Mast Cell Tumor inguinal area IV 10 x 7mm
Results
0h 48h 168h
100
200
300
400
500
600
700
Time
Pla
tele
ts (
cell
sm
mˆ3
)
0h 48h 168h0
1
2
3
4
5
6
7
8
9
Time
RB
C (
x10ˆ6
mm
ˆ3)
0h 48h 168h0
5
10
15
20
25
Time
WB
C (
cell
sm
mˆ3
)
- No difference in PE and clinical parameters- Treatment did no change biochemistry
profile- ALT ALP ALB GLOB Tbil TB- CRE BUN PHOS K+ Na+- AMY PHOS GLU Ca
Results
p=00306
Results
IL-10
Inhibitory actions on macrophages and DC
Inhibits the production of IL-12 and IL-2
Decrease the expression of class II MHC
Produced by- T and B Cells- Monocytes- DC- NK
Stimulation of macrophage phagocytosis and NK cytotoxicity
Carson et al 1995
Moore et al 2001 de Waal et al 1993
Inhibitory effects of IL-10 on tumor growth in animal models
Mocelli et al The dual role of IL-10 2003
Co
ntr
ol
IL-1
0
Mocelli et al The dual role of IL-10 2003
J Interferon Cytokine Res 1999 Jul19(7)697-703Regulation of tumor growth and metastasis by interleukin-10 themelanoma experienceHuang S1 Ullrich SE Bar-Eli M
J Exp Med 1996 Aug 1184(2)579-84Interleukin-10 inhibits tumor metastasis through an NK cell-dependent mechanismZheng LM1 Ojcius DM Garaud F Roth C Maxwell E Li Z Rong H Chen J Wang XY Catino JJ King I
Results
Results
Conclusions
bull Single dose of MCWF (50 μgKg) IV increases IL-10 serum levels 2 hours post-treatment with statistically significant difference (p=00306)
bull Dogs treated with MCWF demonstrated significantly improved quality of lifendash appetite activity level playfulness and general health
improvement
bull The clinical effectiveness against various malignancies potential activation of NK and tumor control in dogs with spontaneous tumors are still undetermined
Study Limitations
bull Small number of dogs
bull No healthy dogs as a control
Future Directions
bull Evaluate the biological activity in patients with solid tumors
bull Compare the cytokine production after local treatment
lucasrodriguesestimavetbrACKNOWLEDGMENT
Mirtes MartisLarissa LosowskiDenise SamiaKaique BrazAna Carolina FariaDaiana SousaFelipe FernandesGraziela SantosElena ToazzaElis MontiCarolina FabriLarissa LopesGiza CabralKladine MoniqueSthefany Chagas
Joyce Ana Paula KarenBarbara Michele CharlesAline Andrade - Gisele Paim
Goal of this Study
The aim of this study was to evaluate the ability of MCWF to induce serum cytokine
synthesis after single intravenous treatment in dogs with different solid tumors
Mycobacterium cell wall fraction (MCWF)
Biological Modulator
Induce cytokine production
Induce apoptosis
Filion et al 1999 Morales et al 2015
Human and canine TCC in vitro HT-1376 HT-1197 and K99
Study Design
10 naiumlve dogs with solid tumors
bull Tumor Diagnosis
bull Complete Staging (3 view Chest X-Ray ABD-US)
bull CBC Biochemistry Urinalysis
bull Body Condition Score and ECOG performance Status
MCWF treatment bull 50μgKg in 100mL of 09NaCl over 45min as slow IV infusion
Cytokine Analysis
Study Design
Pre-treatment
bullPE
bullCBC + Biochemistry
bullUrinalysis
bullCytokines
2 hours
bullPE
bullCytokines
4 hours
bullPE
bullCytokines
6 hours
bullPE
bullCytokines
12 hours
bullPE
bullCytokines
24 hours
bullPE
bullCytokines
48 hours
bullPE
bullCBC
bullCytokines
168 hours
bullPE
bullCBC + Biochemistry
bullUrinalysis
bullCytokines
IL-2 IL-6
IL-10 GM-CSF
IFN-γ TNF-α
IL-12
MyBiosourcereg
Milliplexreg MAPCCYTOMAG-90K-06
450nm Luminexreg 200 and Xpontent (Software)
Study Design
Results
Patient ID Breed Sex Age Weight (Kg) BCS
Patient1 Mixed female spayed 17 870 2
Patient2 Mixed female spayed 13 675 4
Patient3 Mixed female spayed 15 470 4
Patient4 Mixed female spayed 10 1460 4
Patient5 Pit Bull Male intact 7 3400 2
Patient6 Labrador Male castrated 10 3010 4
Patient7 Labrador female spayed 15 3290 4
Patient8 Mixed female spayed 12 685 4
Patient9 Mixed Male Intact 13 1800 4
Patient10French Bulldog female spayed 25 970 5
Results
Patient ID Diagnosis Location Clinical Staging Tumor Size
Patient1 Oral Melanoma left mandible V 20 x 23 mm
Patient2 Mammary Tumor right M5 II 32 x 32 mm
Patient3 Mammary Tumor right M5 II 32 x 30mm
Patient4 Mast Cell Tumor left leg Ia 20 x 18mm
Patient5 Osteosarcoma left femur II 85 x 80mm
Patient6 Oral Melanoma right mandible II 50 x 48mm
Patient7 Hepatocellular Carcinoma left lobe I 472 x 297mm
Patient8 Mammary Tumor right M4 II 33 x 29mm
Patient9 Mast Cell Tumor left leg IV 56 x 42mm
Patient10 Mast Cell Tumor inguinal area IV 10 x 7mm
Results
0h 48h 168h
100
200
300
400
500
600
700
Time
Pla
tele
ts (
cell
sm
mˆ3
)
0h 48h 168h0
1
2
3
4
5
6
7
8
9
Time
RB
C (
x10ˆ6
mm
ˆ3)
0h 48h 168h0
5
10
15
20
25
Time
WB
C (
cell
sm
mˆ3
)
- No difference in PE and clinical parameters- Treatment did no change biochemistry
profile- ALT ALP ALB GLOB Tbil TB- CRE BUN PHOS K+ Na+- AMY PHOS GLU Ca
Results
p=00306
Results
IL-10
Inhibitory actions on macrophages and DC
Inhibits the production of IL-12 and IL-2
Decrease the expression of class II MHC
Produced by- T and B Cells- Monocytes- DC- NK
Stimulation of macrophage phagocytosis and NK cytotoxicity
Carson et al 1995
Moore et al 2001 de Waal et al 1993
Inhibitory effects of IL-10 on tumor growth in animal models
Mocelli et al The dual role of IL-10 2003
Co
ntr
ol
IL-1
0
Mocelli et al The dual role of IL-10 2003
J Interferon Cytokine Res 1999 Jul19(7)697-703Regulation of tumor growth and metastasis by interleukin-10 themelanoma experienceHuang S1 Ullrich SE Bar-Eli M
J Exp Med 1996 Aug 1184(2)579-84Interleukin-10 inhibits tumor metastasis through an NK cell-dependent mechanismZheng LM1 Ojcius DM Garaud F Roth C Maxwell E Li Z Rong H Chen J Wang XY Catino JJ King I
Results
Results
Conclusions
bull Single dose of MCWF (50 μgKg) IV increases IL-10 serum levels 2 hours post-treatment with statistically significant difference (p=00306)
bull Dogs treated with MCWF demonstrated significantly improved quality of lifendash appetite activity level playfulness and general health
improvement
bull The clinical effectiveness against various malignancies potential activation of NK and tumor control in dogs with spontaneous tumors are still undetermined
Study Limitations
bull Small number of dogs
bull No healthy dogs as a control
Future Directions
bull Evaluate the biological activity in patients with solid tumors
bull Compare the cytokine production after local treatment
lucasrodriguesestimavetbrACKNOWLEDGMENT
Mirtes MartisLarissa LosowskiDenise SamiaKaique BrazAna Carolina FariaDaiana SousaFelipe FernandesGraziela SantosElena ToazzaElis MontiCarolina FabriLarissa LopesGiza CabralKladine MoniqueSthefany Chagas
Joyce Ana Paula KarenBarbara Michele CharlesAline Andrade - Gisele Paim
Mycobacterium cell wall fraction (MCWF)
Biological Modulator
Induce cytokine production
Induce apoptosis
Filion et al 1999 Morales et al 2015
Human and canine TCC in vitro HT-1376 HT-1197 and K99
Study Design
10 naiumlve dogs with solid tumors
bull Tumor Diagnosis
bull Complete Staging (3 view Chest X-Ray ABD-US)
bull CBC Biochemistry Urinalysis
bull Body Condition Score and ECOG performance Status
MCWF treatment bull 50μgKg in 100mL of 09NaCl over 45min as slow IV infusion
Cytokine Analysis
Study Design
Pre-treatment
bullPE
bullCBC + Biochemistry
bullUrinalysis
bullCytokines
2 hours
bullPE
bullCytokines
4 hours
bullPE
bullCytokines
6 hours
bullPE
bullCytokines
12 hours
bullPE
bullCytokines
24 hours
bullPE
bullCytokines
48 hours
bullPE
bullCBC
bullCytokines
168 hours
bullPE
bullCBC + Biochemistry
bullUrinalysis
bullCytokines
IL-2 IL-6
IL-10 GM-CSF
IFN-γ TNF-α
IL-12
MyBiosourcereg
Milliplexreg MAPCCYTOMAG-90K-06
450nm Luminexreg 200 and Xpontent (Software)
Study Design
Results
Patient ID Breed Sex Age Weight (Kg) BCS
Patient1 Mixed female spayed 17 870 2
Patient2 Mixed female spayed 13 675 4
Patient3 Mixed female spayed 15 470 4
Patient4 Mixed female spayed 10 1460 4
Patient5 Pit Bull Male intact 7 3400 2
Patient6 Labrador Male castrated 10 3010 4
Patient7 Labrador female spayed 15 3290 4
Patient8 Mixed female spayed 12 685 4
Patient9 Mixed Male Intact 13 1800 4
Patient10French Bulldog female spayed 25 970 5
Results
Patient ID Diagnosis Location Clinical Staging Tumor Size
Patient1 Oral Melanoma left mandible V 20 x 23 mm
Patient2 Mammary Tumor right M5 II 32 x 32 mm
Patient3 Mammary Tumor right M5 II 32 x 30mm
Patient4 Mast Cell Tumor left leg Ia 20 x 18mm
Patient5 Osteosarcoma left femur II 85 x 80mm
Patient6 Oral Melanoma right mandible II 50 x 48mm
Patient7 Hepatocellular Carcinoma left lobe I 472 x 297mm
Patient8 Mammary Tumor right M4 II 33 x 29mm
Patient9 Mast Cell Tumor left leg IV 56 x 42mm
Patient10 Mast Cell Tumor inguinal area IV 10 x 7mm
Results
0h 48h 168h
100
200
300
400
500
600
700
Time
Pla
tele
ts (
cell
sm
mˆ3
)
0h 48h 168h0
1
2
3
4
5
6
7
8
9
Time
RB
C (
x10ˆ6
mm
ˆ3)
0h 48h 168h0
5
10
15
20
25
Time
WB
C (
cell
sm
mˆ3
)
- No difference in PE and clinical parameters- Treatment did no change biochemistry
profile- ALT ALP ALB GLOB Tbil TB- CRE BUN PHOS K+ Na+- AMY PHOS GLU Ca
Results
p=00306
Results
IL-10
Inhibitory actions on macrophages and DC
Inhibits the production of IL-12 and IL-2
Decrease the expression of class II MHC
Produced by- T and B Cells- Monocytes- DC- NK
Stimulation of macrophage phagocytosis and NK cytotoxicity
Carson et al 1995
Moore et al 2001 de Waal et al 1993
Inhibitory effects of IL-10 on tumor growth in animal models
Mocelli et al The dual role of IL-10 2003
Co
ntr
ol
IL-1
0
Mocelli et al The dual role of IL-10 2003
J Interferon Cytokine Res 1999 Jul19(7)697-703Regulation of tumor growth and metastasis by interleukin-10 themelanoma experienceHuang S1 Ullrich SE Bar-Eli M
J Exp Med 1996 Aug 1184(2)579-84Interleukin-10 inhibits tumor metastasis through an NK cell-dependent mechanismZheng LM1 Ojcius DM Garaud F Roth C Maxwell E Li Z Rong H Chen J Wang XY Catino JJ King I
Results
Results
Conclusions
bull Single dose of MCWF (50 μgKg) IV increases IL-10 serum levels 2 hours post-treatment with statistically significant difference (p=00306)
bull Dogs treated with MCWF demonstrated significantly improved quality of lifendash appetite activity level playfulness and general health
improvement
bull The clinical effectiveness against various malignancies potential activation of NK and tumor control in dogs with spontaneous tumors are still undetermined
Study Limitations
bull Small number of dogs
bull No healthy dogs as a control
Future Directions
bull Evaluate the biological activity in patients with solid tumors
bull Compare the cytokine production after local treatment
lucasrodriguesestimavetbrACKNOWLEDGMENT
Mirtes MartisLarissa LosowskiDenise SamiaKaique BrazAna Carolina FariaDaiana SousaFelipe FernandesGraziela SantosElena ToazzaElis MontiCarolina FabriLarissa LopesGiza CabralKladine MoniqueSthefany Chagas
Joyce Ana Paula KarenBarbara Michele CharlesAline Andrade - Gisele Paim
Study Design
10 naiumlve dogs with solid tumors
bull Tumor Diagnosis
bull Complete Staging (3 view Chest X-Ray ABD-US)
bull CBC Biochemistry Urinalysis
bull Body Condition Score and ECOG performance Status
MCWF treatment bull 50μgKg in 100mL of 09NaCl over 45min as slow IV infusion
Cytokine Analysis
Study Design
Pre-treatment
bullPE
bullCBC + Biochemistry
bullUrinalysis
bullCytokines
2 hours
bullPE
bullCytokines
4 hours
bullPE
bullCytokines
6 hours
bullPE
bullCytokines
12 hours
bullPE
bullCytokines
24 hours
bullPE
bullCytokines
48 hours
bullPE
bullCBC
bullCytokines
168 hours
bullPE
bullCBC + Biochemistry
bullUrinalysis
bullCytokines
IL-2 IL-6
IL-10 GM-CSF
IFN-γ TNF-α
IL-12
MyBiosourcereg
Milliplexreg MAPCCYTOMAG-90K-06
450nm Luminexreg 200 and Xpontent (Software)
Study Design
Results
Patient ID Breed Sex Age Weight (Kg) BCS
Patient1 Mixed female spayed 17 870 2
Patient2 Mixed female spayed 13 675 4
Patient3 Mixed female spayed 15 470 4
Patient4 Mixed female spayed 10 1460 4
Patient5 Pit Bull Male intact 7 3400 2
Patient6 Labrador Male castrated 10 3010 4
Patient7 Labrador female spayed 15 3290 4
Patient8 Mixed female spayed 12 685 4
Patient9 Mixed Male Intact 13 1800 4
Patient10French Bulldog female spayed 25 970 5
Results
Patient ID Diagnosis Location Clinical Staging Tumor Size
Patient1 Oral Melanoma left mandible V 20 x 23 mm
Patient2 Mammary Tumor right M5 II 32 x 32 mm
Patient3 Mammary Tumor right M5 II 32 x 30mm
Patient4 Mast Cell Tumor left leg Ia 20 x 18mm
Patient5 Osteosarcoma left femur II 85 x 80mm
Patient6 Oral Melanoma right mandible II 50 x 48mm
Patient7 Hepatocellular Carcinoma left lobe I 472 x 297mm
Patient8 Mammary Tumor right M4 II 33 x 29mm
Patient9 Mast Cell Tumor left leg IV 56 x 42mm
Patient10 Mast Cell Tumor inguinal area IV 10 x 7mm
Results
0h 48h 168h
100
200
300
400
500
600
700
Time
Pla
tele
ts (
cell
sm
mˆ3
)
0h 48h 168h0
1
2
3
4
5
6
7
8
9
Time
RB
C (
x10ˆ6
mm
ˆ3)
0h 48h 168h0
5
10
15
20
25
Time
WB
C (
cell
sm
mˆ3
)
- No difference in PE and clinical parameters- Treatment did no change biochemistry
profile- ALT ALP ALB GLOB Tbil TB- CRE BUN PHOS K+ Na+- AMY PHOS GLU Ca
Results
p=00306
Results
IL-10
Inhibitory actions on macrophages and DC
Inhibits the production of IL-12 and IL-2
Decrease the expression of class II MHC
Produced by- T and B Cells- Monocytes- DC- NK
Stimulation of macrophage phagocytosis and NK cytotoxicity
Carson et al 1995
Moore et al 2001 de Waal et al 1993
Inhibitory effects of IL-10 on tumor growth in animal models
Mocelli et al The dual role of IL-10 2003
Co
ntr
ol
IL-1
0
Mocelli et al The dual role of IL-10 2003
J Interferon Cytokine Res 1999 Jul19(7)697-703Regulation of tumor growth and metastasis by interleukin-10 themelanoma experienceHuang S1 Ullrich SE Bar-Eli M
J Exp Med 1996 Aug 1184(2)579-84Interleukin-10 inhibits tumor metastasis through an NK cell-dependent mechanismZheng LM1 Ojcius DM Garaud F Roth C Maxwell E Li Z Rong H Chen J Wang XY Catino JJ King I
Results
Results
Conclusions
bull Single dose of MCWF (50 μgKg) IV increases IL-10 serum levels 2 hours post-treatment with statistically significant difference (p=00306)
bull Dogs treated with MCWF demonstrated significantly improved quality of lifendash appetite activity level playfulness and general health
improvement
bull The clinical effectiveness against various malignancies potential activation of NK and tumor control in dogs with spontaneous tumors are still undetermined
Study Limitations
bull Small number of dogs
bull No healthy dogs as a control
Future Directions
bull Evaluate the biological activity in patients with solid tumors
bull Compare the cytokine production after local treatment
lucasrodriguesestimavetbrACKNOWLEDGMENT
Mirtes MartisLarissa LosowskiDenise SamiaKaique BrazAna Carolina FariaDaiana SousaFelipe FernandesGraziela SantosElena ToazzaElis MontiCarolina FabriLarissa LopesGiza CabralKladine MoniqueSthefany Chagas
Joyce Ana Paula KarenBarbara Michele CharlesAline Andrade - Gisele Paim
Study Design
Pre-treatment
bullPE
bullCBC + Biochemistry
bullUrinalysis
bullCytokines
2 hours
bullPE
bullCytokines
4 hours
bullPE
bullCytokines
6 hours
bullPE
bullCytokines
12 hours
bullPE
bullCytokines
24 hours
bullPE
bullCytokines
48 hours
bullPE
bullCBC
bullCytokines
168 hours
bullPE
bullCBC + Biochemistry
bullUrinalysis
bullCytokines
IL-2 IL-6
IL-10 GM-CSF
IFN-γ TNF-α
IL-12
MyBiosourcereg
Milliplexreg MAPCCYTOMAG-90K-06
450nm Luminexreg 200 and Xpontent (Software)
Study Design
Results
Patient ID Breed Sex Age Weight (Kg) BCS
Patient1 Mixed female spayed 17 870 2
Patient2 Mixed female spayed 13 675 4
Patient3 Mixed female spayed 15 470 4
Patient4 Mixed female spayed 10 1460 4
Patient5 Pit Bull Male intact 7 3400 2
Patient6 Labrador Male castrated 10 3010 4
Patient7 Labrador female spayed 15 3290 4
Patient8 Mixed female spayed 12 685 4
Patient9 Mixed Male Intact 13 1800 4
Patient10French Bulldog female spayed 25 970 5
Results
Patient ID Diagnosis Location Clinical Staging Tumor Size
Patient1 Oral Melanoma left mandible V 20 x 23 mm
Patient2 Mammary Tumor right M5 II 32 x 32 mm
Patient3 Mammary Tumor right M5 II 32 x 30mm
Patient4 Mast Cell Tumor left leg Ia 20 x 18mm
Patient5 Osteosarcoma left femur II 85 x 80mm
Patient6 Oral Melanoma right mandible II 50 x 48mm
Patient7 Hepatocellular Carcinoma left lobe I 472 x 297mm
Patient8 Mammary Tumor right M4 II 33 x 29mm
Patient9 Mast Cell Tumor left leg IV 56 x 42mm
Patient10 Mast Cell Tumor inguinal area IV 10 x 7mm
Results
0h 48h 168h
100
200
300
400
500
600
700
Time
Pla
tele
ts (
cell
sm
mˆ3
)
0h 48h 168h0
1
2
3
4
5
6
7
8
9
Time
RB
C (
x10ˆ6
mm
ˆ3)
0h 48h 168h0
5
10
15
20
25
Time
WB
C (
cell
sm
mˆ3
)
- No difference in PE and clinical parameters- Treatment did no change biochemistry
profile- ALT ALP ALB GLOB Tbil TB- CRE BUN PHOS K+ Na+- AMY PHOS GLU Ca
Results
p=00306
Results
IL-10
Inhibitory actions on macrophages and DC
Inhibits the production of IL-12 and IL-2
Decrease the expression of class II MHC
Produced by- T and B Cells- Monocytes- DC- NK
Stimulation of macrophage phagocytosis and NK cytotoxicity
Carson et al 1995
Moore et al 2001 de Waal et al 1993
Inhibitory effects of IL-10 on tumor growth in animal models
Mocelli et al The dual role of IL-10 2003
Co
ntr
ol
IL-1
0
Mocelli et al The dual role of IL-10 2003
J Interferon Cytokine Res 1999 Jul19(7)697-703Regulation of tumor growth and metastasis by interleukin-10 themelanoma experienceHuang S1 Ullrich SE Bar-Eli M
J Exp Med 1996 Aug 1184(2)579-84Interleukin-10 inhibits tumor metastasis through an NK cell-dependent mechanismZheng LM1 Ojcius DM Garaud F Roth C Maxwell E Li Z Rong H Chen J Wang XY Catino JJ King I
Results
Results
Conclusions
bull Single dose of MCWF (50 μgKg) IV increases IL-10 serum levels 2 hours post-treatment with statistically significant difference (p=00306)
bull Dogs treated with MCWF demonstrated significantly improved quality of lifendash appetite activity level playfulness and general health
improvement
bull The clinical effectiveness against various malignancies potential activation of NK and tumor control in dogs with spontaneous tumors are still undetermined
Study Limitations
bull Small number of dogs
bull No healthy dogs as a control
Future Directions
bull Evaluate the biological activity in patients with solid tumors
bull Compare the cytokine production after local treatment
lucasrodriguesestimavetbrACKNOWLEDGMENT
Mirtes MartisLarissa LosowskiDenise SamiaKaique BrazAna Carolina FariaDaiana SousaFelipe FernandesGraziela SantosElena ToazzaElis MontiCarolina FabriLarissa LopesGiza CabralKladine MoniqueSthefany Chagas
Joyce Ana Paula KarenBarbara Michele CharlesAline Andrade - Gisele Paim
IL-2 IL-6
IL-10 GM-CSF
IFN-γ TNF-α
IL-12
MyBiosourcereg
Milliplexreg MAPCCYTOMAG-90K-06
450nm Luminexreg 200 and Xpontent (Software)
Study Design
Results
Patient ID Breed Sex Age Weight (Kg) BCS
Patient1 Mixed female spayed 17 870 2
Patient2 Mixed female spayed 13 675 4
Patient3 Mixed female spayed 15 470 4
Patient4 Mixed female spayed 10 1460 4
Patient5 Pit Bull Male intact 7 3400 2
Patient6 Labrador Male castrated 10 3010 4
Patient7 Labrador female spayed 15 3290 4
Patient8 Mixed female spayed 12 685 4
Patient9 Mixed Male Intact 13 1800 4
Patient10French Bulldog female spayed 25 970 5
Results
Patient ID Diagnosis Location Clinical Staging Tumor Size
Patient1 Oral Melanoma left mandible V 20 x 23 mm
Patient2 Mammary Tumor right M5 II 32 x 32 mm
Patient3 Mammary Tumor right M5 II 32 x 30mm
Patient4 Mast Cell Tumor left leg Ia 20 x 18mm
Patient5 Osteosarcoma left femur II 85 x 80mm
Patient6 Oral Melanoma right mandible II 50 x 48mm
Patient7 Hepatocellular Carcinoma left lobe I 472 x 297mm
Patient8 Mammary Tumor right M4 II 33 x 29mm
Patient9 Mast Cell Tumor left leg IV 56 x 42mm
Patient10 Mast Cell Tumor inguinal area IV 10 x 7mm
Results
0h 48h 168h
100
200
300
400
500
600
700
Time
Pla
tele
ts (
cell
sm
mˆ3
)
0h 48h 168h0
1
2
3
4
5
6
7
8
9
Time
RB
C (
x10ˆ6
mm
ˆ3)
0h 48h 168h0
5
10
15
20
25
Time
WB
C (
cell
sm
mˆ3
)
- No difference in PE and clinical parameters- Treatment did no change biochemistry
profile- ALT ALP ALB GLOB Tbil TB- CRE BUN PHOS K+ Na+- AMY PHOS GLU Ca
Results
p=00306
Results
IL-10
Inhibitory actions on macrophages and DC
Inhibits the production of IL-12 and IL-2
Decrease the expression of class II MHC
Produced by- T and B Cells- Monocytes- DC- NK
Stimulation of macrophage phagocytosis and NK cytotoxicity
Carson et al 1995
Moore et al 2001 de Waal et al 1993
Inhibitory effects of IL-10 on tumor growth in animal models
Mocelli et al The dual role of IL-10 2003
Co
ntr
ol
IL-1
0
Mocelli et al The dual role of IL-10 2003
J Interferon Cytokine Res 1999 Jul19(7)697-703Regulation of tumor growth and metastasis by interleukin-10 themelanoma experienceHuang S1 Ullrich SE Bar-Eli M
J Exp Med 1996 Aug 1184(2)579-84Interleukin-10 inhibits tumor metastasis through an NK cell-dependent mechanismZheng LM1 Ojcius DM Garaud F Roth C Maxwell E Li Z Rong H Chen J Wang XY Catino JJ King I
Results
Results
Conclusions
bull Single dose of MCWF (50 μgKg) IV increases IL-10 serum levels 2 hours post-treatment with statistically significant difference (p=00306)
bull Dogs treated with MCWF demonstrated significantly improved quality of lifendash appetite activity level playfulness and general health
improvement
bull The clinical effectiveness against various malignancies potential activation of NK and tumor control in dogs with spontaneous tumors are still undetermined
Study Limitations
bull Small number of dogs
bull No healthy dogs as a control
Future Directions
bull Evaluate the biological activity in patients with solid tumors
bull Compare the cytokine production after local treatment
lucasrodriguesestimavetbrACKNOWLEDGMENT
Mirtes MartisLarissa LosowskiDenise SamiaKaique BrazAna Carolina FariaDaiana SousaFelipe FernandesGraziela SantosElena ToazzaElis MontiCarolina FabriLarissa LopesGiza CabralKladine MoniqueSthefany Chagas
Joyce Ana Paula KarenBarbara Michele CharlesAline Andrade - Gisele Paim
Results
Patient ID Breed Sex Age Weight (Kg) BCS
Patient1 Mixed female spayed 17 870 2
Patient2 Mixed female spayed 13 675 4
Patient3 Mixed female spayed 15 470 4
Patient4 Mixed female spayed 10 1460 4
Patient5 Pit Bull Male intact 7 3400 2
Patient6 Labrador Male castrated 10 3010 4
Patient7 Labrador female spayed 15 3290 4
Patient8 Mixed female spayed 12 685 4
Patient9 Mixed Male Intact 13 1800 4
Patient10French Bulldog female spayed 25 970 5
Results
Patient ID Diagnosis Location Clinical Staging Tumor Size
Patient1 Oral Melanoma left mandible V 20 x 23 mm
Patient2 Mammary Tumor right M5 II 32 x 32 mm
Patient3 Mammary Tumor right M5 II 32 x 30mm
Patient4 Mast Cell Tumor left leg Ia 20 x 18mm
Patient5 Osteosarcoma left femur II 85 x 80mm
Patient6 Oral Melanoma right mandible II 50 x 48mm
Patient7 Hepatocellular Carcinoma left lobe I 472 x 297mm
Patient8 Mammary Tumor right M4 II 33 x 29mm
Patient9 Mast Cell Tumor left leg IV 56 x 42mm
Patient10 Mast Cell Tumor inguinal area IV 10 x 7mm
Results
0h 48h 168h
100
200
300
400
500
600
700
Time
Pla
tele
ts (
cell
sm
mˆ3
)
0h 48h 168h0
1
2
3
4
5
6
7
8
9
Time
RB
C (
x10ˆ6
mm
ˆ3)
0h 48h 168h0
5
10
15
20
25
Time
WB
C (
cell
sm
mˆ3
)
- No difference in PE and clinical parameters- Treatment did no change biochemistry
profile- ALT ALP ALB GLOB Tbil TB- CRE BUN PHOS K+ Na+- AMY PHOS GLU Ca
Results
p=00306
Results
IL-10
Inhibitory actions on macrophages and DC
Inhibits the production of IL-12 and IL-2
Decrease the expression of class II MHC
Produced by- T and B Cells- Monocytes- DC- NK
Stimulation of macrophage phagocytosis and NK cytotoxicity
Carson et al 1995
Moore et al 2001 de Waal et al 1993
Inhibitory effects of IL-10 on tumor growth in animal models
Mocelli et al The dual role of IL-10 2003
Co
ntr
ol
IL-1
0
Mocelli et al The dual role of IL-10 2003
J Interferon Cytokine Res 1999 Jul19(7)697-703Regulation of tumor growth and metastasis by interleukin-10 themelanoma experienceHuang S1 Ullrich SE Bar-Eli M
J Exp Med 1996 Aug 1184(2)579-84Interleukin-10 inhibits tumor metastasis through an NK cell-dependent mechanismZheng LM1 Ojcius DM Garaud F Roth C Maxwell E Li Z Rong H Chen J Wang XY Catino JJ King I
Results
Results
Conclusions
bull Single dose of MCWF (50 μgKg) IV increases IL-10 serum levels 2 hours post-treatment with statistically significant difference (p=00306)
bull Dogs treated with MCWF demonstrated significantly improved quality of lifendash appetite activity level playfulness and general health
improvement
bull The clinical effectiveness against various malignancies potential activation of NK and tumor control in dogs with spontaneous tumors are still undetermined
Study Limitations
bull Small number of dogs
bull No healthy dogs as a control
Future Directions
bull Evaluate the biological activity in patients with solid tumors
bull Compare the cytokine production after local treatment
lucasrodriguesestimavetbrACKNOWLEDGMENT
Mirtes MartisLarissa LosowskiDenise SamiaKaique BrazAna Carolina FariaDaiana SousaFelipe FernandesGraziela SantosElena ToazzaElis MontiCarolina FabriLarissa LopesGiza CabralKladine MoniqueSthefany Chagas
Joyce Ana Paula KarenBarbara Michele CharlesAline Andrade - Gisele Paim
Results
Patient ID Diagnosis Location Clinical Staging Tumor Size
Patient1 Oral Melanoma left mandible V 20 x 23 mm
Patient2 Mammary Tumor right M5 II 32 x 32 mm
Patient3 Mammary Tumor right M5 II 32 x 30mm
Patient4 Mast Cell Tumor left leg Ia 20 x 18mm
Patient5 Osteosarcoma left femur II 85 x 80mm
Patient6 Oral Melanoma right mandible II 50 x 48mm
Patient7 Hepatocellular Carcinoma left lobe I 472 x 297mm
Patient8 Mammary Tumor right M4 II 33 x 29mm
Patient9 Mast Cell Tumor left leg IV 56 x 42mm
Patient10 Mast Cell Tumor inguinal area IV 10 x 7mm
Results
0h 48h 168h
100
200
300
400
500
600
700
Time
Pla
tele
ts (
cell
sm
mˆ3
)
0h 48h 168h0
1
2
3
4
5
6
7
8
9
Time
RB
C (
x10ˆ6
mm
ˆ3)
0h 48h 168h0
5
10
15
20
25
Time
WB
C (
cell
sm
mˆ3
)
- No difference in PE and clinical parameters- Treatment did no change biochemistry
profile- ALT ALP ALB GLOB Tbil TB- CRE BUN PHOS K+ Na+- AMY PHOS GLU Ca
Results
p=00306
Results
IL-10
Inhibitory actions on macrophages and DC
Inhibits the production of IL-12 and IL-2
Decrease the expression of class II MHC
Produced by- T and B Cells- Monocytes- DC- NK
Stimulation of macrophage phagocytosis and NK cytotoxicity
Carson et al 1995
Moore et al 2001 de Waal et al 1993
Inhibitory effects of IL-10 on tumor growth in animal models
Mocelli et al The dual role of IL-10 2003
Co
ntr
ol
IL-1
0
Mocelli et al The dual role of IL-10 2003
J Interferon Cytokine Res 1999 Jul19(7)697-703Regulation of tumor growth and metastasis by interleukin-10 themelanoma experienceHuang S1 Ullrich SE Bar-Eli M
J Exp Med 1996 Aug 1184(2)579-84Interleukin-10 inhibits tumor metastasis through an NK cell-dependent mechanismZheng LM1 Ojcius DM Garaud F Roth C Maxwell E Li Z Rong H Chen J Wang XY Catino JJ King I
Results
Results
Conclusions
bull Single dose of MCWF (50 μgKg) IV increases IL-10 serum levels 2 hours post-treatment with statistically significant difference (p=00306)
bull Dogs treated with MCWF demonstrated significantly improved quality of lifendash appetite activity level playfulness and general health
improvement
bull The clinical effectiveness against various malignancies potential activation of NK and tumor control in dogs with spontaneous tumors are still undetermined
Study Limitations
bull Small number of dogs
bull No healthy dogs as a control
Future Directions
bull Evaluate the biological activity in patients with solid tumors
bull Compare the cytokine production after local treatment
lucasrodriguesestimavetbrACKNOWLEDGMENT
Mirtes MartisLarissa LosowskiDenise SamiaKaique BrazAna Carolina FariaDaiana SousaFelipe FernandesGraziela SantosElena ToazzaElis MontiCarolina FabriLarissa LopesGiza CabralKladine MoniqueSthefany Chagas
Joyce Ana Paula KarenBarbara Michele CharlesAline Andrade - Gisele Paim
Results
0h 48h 168h
100
200
300
400
500
600
700
Time
Pla
tele
ts (
cell
sm
mˆ3
)
0h 48h 168h0
1
2
3
4
5
6
7
8
9
Time
RB
C (
x10ˆ6
mm
ˆ3)
0h 48h 168h0
5
10
15
20
25
Time
WB
C (
cell
sm
mˆ3
)
- No difference in PE and clinical parameters- Treatment did no change biochemistry
profile- ALT ALP ALB GLOB Tbil TB- CRE BUN PHOS K+ Na+- AMY PHOS GLU Ca
Results
p=00306
Results
IL-10
Inhibitory actions on macrophages and DC
Inhibits the production of IL-12 and IL-2
Decrease the expression of class II MHC
Produced by- T and B Cells- Monocytes- DC- NK
Stimulation of macrophage phagocytosis and NK cytotoxicity
Carson et al 1995
Moore et al 2001 de Waal et al 1993
Inhibitory effects of IL-10 on tumor growth in animal models
Mocelli et al The dual role of IL-10 2003
Co
ntr
ol
IL-1
0
Mocelli et al The dual role of IL-10 2003
J Interferon Cytokine Res 1999 Jul19(7)697-703Regulation of tumor growth and metastasis by interleukin-10 themelanoma experienceHuang S1 Ullrich SE Bar-Eli M
J Exp Med 1996 Aug 1184(2)579-84Interleukin-10 inhibits tumor metastasis through an NK cell-dependent mechanismZheng LM1 Ojcius DM Garaud F Roth C Maxwell E Li Z Rong H Chen J Wang XY Catino JJ King I
Results
Results
Conclusions
bull Single dose of MCWF (50 μgKg) IV increases IL-10 serum levels 2 hours post-treatment with statistically significant difference (p=00306)
bull Dogs treated with MCWF demonstrated significantly improved quality of lifendash appetite activity level playfulness and general health
improvement
bull The clinical effectiveness against various malignancies potential activation of NK and tumor control in dogs with spontaneous tumors are still undetermined
Study Limitations
bull Small number of dogs
bull No healthy dogs as a control
Future Directions
bull Evaluate the biological activity in patients with solid tumors
bull Compare the cytokine production after local treatment
lucasrodriguesestimavetbrACKNOWLEDGMENT
Mirtes MartisLarissa LosowskiDenise SamiaKaique BrazAna Carolina FariaDaiana SousaFelipe FernandesGraziela SantosElena ToazzaElis MontiCarolina FabriLarissa LopesGiza CabralKladine MoniqueSthefany Chagas
Joyce Ana Paula KarenBarbara Michele CharlesAline Andrade - Gisele Paim
Results
p=00306
Results
IL-10
Inhibitory actions on macrophages and DC
Inhibits the production of IL-12 and IL-2
Decrease the expression of class II MHC
Produced by- T and B Cells- Monocytes- DC- NK
Stimulation of macrophage phagocytosis and NK cytotoxicity
Carson et al 1995
Moore et al 2001 de Waal et al 1993
Inhibitory effects of IL-10 on tumor growth in animal models
Mocelli et al The dual role of IL-10 2003
Co
ntr
ol
IL-1
0
Mocelli et al The dual role of IL-10 2003
J Interferon Cytokine Res 1999 Jul19(7)697-703Regulation of tumor growth and metastasis by interleukin-10 themelanoma experienceHuang S1 Ullrich SE Bar-Eli M
J Exp Med 1996 Aug 1184(2)579-84Interleukin-10 inhibits tumor metastasis through an NK cell-dependent mechanismZheng LM1 Ojcius DM Garaud F Roth C Maxwell E Li Z Rong H Chen J Wang XY Catino JJ King I
Results
Results
Conclusions
bull Single dose of MCWF (50 μgKg) IV increases IL-10 serum levels 2 hours post-treatment with statistically significant difference (p=00306)
bull Dogs treated with MCWF demonstrated significantly improved quality of lifendash appetite activity level playfulness and general health
improvement
bull The clinical effectiveness against various malignancies potential activation of NK and tumor control in dogs with spontaneous tumors are still undetermined
Study Limitations
bull Small number of dogs
bull No healthy dogs as a control
Future Directions
bull Evaluate the biological activity in patients with solid tumors
bull Compare the cytokine production after local treatment
lucasrodriguesestimavetbrACKNOWLEDGMENT
Mirtes MartisLarissa LosowskiDenise SamiaKaique BrazAna Carolina FariaDaiana SousaFelipe FernandesGraziela SantosElena ToazzaElis MontiCarolina FabriLarissa LopesGiza CabralKladine MoniqueSthefany Chagas
Joyce Ana Paula KarenBarbara Michele CharlesAline Andrade - Gisele Paim
Results
IL-10
Inhibitory actions on macrophages and DC
Inhibits the production of IL-12 and IL-2
Decrease the expression of class II MHC
Produced by- T and B Cells- Monocytes- DC- NK
Stimulation of macrophage phagocytosis and NK cytotoxicity
Carson et al 1995
Moore et al 2001 de Waal et al 1993
Inhibitory effects of IL-10 on tumor growth in animal models
Mocelli et al The dual role of IL-10 2003
Co
ntr
ol
IL-1
0
Mocelli et al The dual role of IL-10 2003
J Interferon Cytokine Res 1999 Jul19(7)697-703Regulation of tumor growth and metastasis by interleukin-10 themelanoma experienceHuang S1 Ullrich SE Bar-Eli M
J Exp Med 1996 Aug 1184(2)579-84Interleukin-10 inhibits tumor metastasis through an NK cell-dependent mechanismZheng LM1 Ojcius DM Garaud F Roth C Maxwell E Li Z Rong H Chen J Wang XY Catino JJ King I
Results
Results
Conclusions
bull Single dose of MCWF (50 μgKg) IV increases IL-10 serum levels 2 hours post-treatment with statistically significant difference (p=00306)
bull Dogs treated with MCWF demonstrated significantly improved quality of lifendash appetite activity level playfulness and general health
improvement
bull The clinical effectiveness against various malignancies potential activation of NK and tumor control in dogs with spontaneous tumors are still undetermined
Study Limitations
bull Small number of dogs
bull No healthy dogs as a control
Future Directions
bull Evaluate the biological activity in patients with solid tumors
bull Compare the cytokine production after local treatment
lucasrodriguesestimavetbrACKNOWLEDGMENT
Mirtes MartisLarissa LosowskiDenise SamiaKaique BrazAna Carolina FariaDaiana SousaFelipe FernandesGraziela SantosElena ToazzaElis MontiCarolina FabriLarissa LopesGiza CabralKladine MoniqueSthefany Chagas
Joyce Ana Paula KarenBarbara Michele CharlesAline Andrade - Gisele Paim
IL-10
Inhibitory actions on macrophages and DC
Inhibits the production of IL-12 and IL-2
Decrease the expression of class II MHC
Produced by- T and B Cells- Monocytes- DC- NK
Stimulation of macrophage phagocytosis and NK cytotoxicity
Carson et al 1995
Moore et al 2001 de Waal et al 1993
Inhibitory effects of IL-10 on tumor growth in animal models
Mocelli et al The dual role of IL-10 2003
Co
ntr
ol
IL-1
0
Mocelli et al The dual role of IL-10 2003
J Interferon Cytokine Res 1999 Jul19(7)697-703Regulation of tumor growth and metastasis by interleukin-10 themelanoma experienceHuang S1 Ullrich SE Bar-Eli M
J Exp Med 1996 Aug 1184(2)579-84Interleukin-10 inhibits tumor metastasis through an NK cell-dependent mechanismZheng LM1 Ojcius DM Garaud F Roth C Maxwell E Li Z Rong H Chen J Wang XY Catino JJ King I
Results
Results
Conclusions
bull Single dose of MCWF (50 μgKg) IV increases IL-10 serum levels 2 hours post-treatment with statistically significant difference (p=00306)
bull Dogs treated with MCWF demonstrated significantly improved quality of lifendash appetite activity level playfulness and general health
improvement
bull The clinical effectiveness against various malignancies potential activation of NK and tumor control in dogs with spontaneous tumors are still undetermined
Study Limitations
bull Small number of dogs
bull No healthy dogs as a control
Future Directions
bull Evaluate the biological activity in patients with solid tumors
bull Compare the cytokine production after local treatment
lucasrodriguesestimavetbrACKNOWLEDGMENT
Mirtes MartisLarissa LosowskiDenise SamiaKaique BrazAna Carolina FariaDaiana SousaFelipe FernandesGraziela SantosElena ToazzaElis MontiCarolina FabriLarissa LopesGiza CabralKladine MoniqueSthefany Chagas
Joyce Ana Paula KarenBarbara Michele CharlesAline Andrade - Gisele Paim
Inhibitory effects of IL-10 on tumor growth in animal models
Mocelli et al The dual role of IL-10 2003
Co
ntr
ol
IL-1
0
Mocelli et al The dual role of IL-10 2003
J Interferon Cytokine Res 1999 Jul19(7)697-703Regulation of tumor growth and metastasis by interleukin-10 themelanoma experienceHuang S1 Ullrich SE Bar-Eli M
J Exp Med 1996 Aug 1184(2)579-84Interleukin-10 inhibits tumor metastasis through an NK cell-dependent mechanismZheng LM1 Ojcius DM Garaud F Roth C Maxwell E Li Z Rong H Chen J Wang XY Catino JJ King I
Results
Results
Conclusions
bull Single dose of MCWF (50 μgKg) IV increases IL-10 serum levels 2 hours post-treatment with statistically significant difference (p=00306)
bull Dogs treated with MCWF demonstrated significantly improved quality of lifendash appetite activity level playfulness and general health
improvement
bull The clinical effectiveness against various malignancies potential activation of NK and tumor control in dogs with spontaneous tumors are still undetermined
Study Limitations
bull Small number of dogs
bull No healthy dogs as a control
Future Directions
bull Evaluate the biological activity in patients with solid tumors
bull Compare the cytokine production after local treatment
lucasrodriguesestimavetbrACKNOWLEDGMENT
Mirtes MartisLarissa LosowskiDenise SamiaKaique BrazAna Carolina FariaDaiana SousaFelipe FernandesGraziela SantosElena ToazzaElis MontiCarolina FabriLarissa LopesGiza CabralKladine MoniqueSthefany Chagas
Joyce Ana Paula KarenBarbara Michele CharlesAline Andrade - Gisele Paim
Co
ntr
ol
IL-1
0
Mocelli et al The dual role of IL-10 2003
J Interferon Cytokine Res 1999 Jul19(7)697-703Regulation of tumor growth and metastasis by interleukin-10 themelanoma experienceHuang S1 Ullrich SE Bar-Eli M
J Exp Med 1996 Aug 1184(2)579-84Interleukin-10 inhibits tumor metastasis through an NK cell-dependent mechanismZheng LM1 Ojcius DM Garaud F Roth C Maxwell E Li Z Rong H Chen J Wang XY Catino JJ King I
Results
Results
Conclusions
bull Single dose of MCWF (50 μgKg) IV increases IL-10 serum levels 2 hours post-treatment with statistically significant difference (p=00306)
bull Dogs treated with MCWF demonstrated significantly improved quality of lifendash appetite activity level playfulness and general health
improvement
bull The clinical effectiveness against various malignancies potential activation of NK and tumor control in dogs with spontaneous tumors are still undetermined
Study Limitations
bull Small number of dogs
bull No healthy dogs as a control
Future Directions
bull Evaluate the biological activity in patients with solid tumors
bull Compare the cytokine production after local treatment
lucasrodriguesestimavetbrACKNOWLEDGMENT
Mirtes MartisLarissa LosowskiDenise SamiaKaique BrazAna Carolina FariaDaiana SousaFelipe FernandesGraziela SantosElena ToazzaElis MontiCarolina FabriLarissa LopesGiza CabralKladine MoniqueSthefany Chagas
Joyce Ana Paula KarenBarbara Michele CharlesAline Andrade - Gisele Paim
Results
Results
Conclusions
bull Single dose of MCWF (50 μgKg) IV increases IL-10 serum levels 2 hours post-treatment with statistically significant difference (p=00306)
bull Dogs treated with MCWF demonstrated significantly improved quality of lifendash appetite activity level playfulness and general health
improvement
bull The clinical effectiveness against various malignancies potential activation of NK and tumor control in dogs with spontaneous tumors are still undetermined
Study Limitations
bull Small number of dogs
bull No healthy dogs as a control
Future Directions
bull Evaluate the biological activity in patients with solid tumors
bull Compare the cytokine production after local treatment
lucasrodriguesestimavetbrACKNOWLEDGMENT
Mirtes MartisLarissa LosowskiDenise SamiaKaique BrazAna Carolina FariaDaiana SousaFelipe FernandesGraziela SantosElena ToazzaElis MontiCarolina FabriLarissa LopesGiza CabralKladine MoniqueSthefany Chagas
Joyce Ana Paula KarenBarbara Michele CharlesAline Andrade - Gisele Paim
Results
Conclusions
bull Single dose of MCWF (50 μgKg) IV increases IL-10 serum levels 2 hours post-treatment with statistically significant difference (p=00306)
bull Dogs treated with MCWF demonstrated significantly improved quality of lifendash appetite activity level playfulness and general health
improvement
bull The clinical effectiveness against various malignancies potential activation of NK and tumor control in dogs with spontaneous tumors are still undetermined
Study Limitations
bull Small number of dogs
bull No healthy dogs as a control
Future Directions
bull Evaluate the biological activity in patients with solid tumors
bull Compare the cytokine production after local treatment
lucasrodriguesestimavetbrACKNOWLEDGMENT
Mirtes MartisLarissa LosowskiDenise SamiaKaique BrazAna Carolina FariaDaiana SousaFelipe FernandesGraziela SantosElena ToazzaElis MontiCarolina FabriLarissa LopesGiza CabralKladine MoniqueSthefany Chagas
Joyce Ana Paula KarenBarbara Michele CharlesAline Andrade - Gisele Paim
Conclusions
bull Single dose of MCWF (50 μgKg) IV increases IL-10 serum levels 2 hours post-treatment with statistically significant difference (p=00306)
bull Dogs treated with MCWF demonstrated significantly improved quality of lifendash appetite activity level playfulness and general health
improvement
bull The clinical effectiveness against various malignancies potential activation of NK and tumor control in dogs with spontaneous tumors are still undetermined
Study Limitations
bull Small number of dogs
bull No healthy dogs as a control
Future Directions
bull Evaluate the biological activity in patients with solid tumors
bull Compare the cytokine production after local treatment
lucasrodriguesestimavetbrACKNOWLEDGMENT
Mirtes MartisLarissa LosowskiDenise SamiaKaique BrazAna Carolina FariaDaiana SousaFelipe FernandesGraziela SantosElena ToazzaElis MontiCarolina FabriLarissa LopesGiza CabralKladine MoniqueSthefany Chagas
Joyce Ana Paula KarenBarbara Michele CharlesAline Andrade - Gisele Paim
Study Limitations
bull Small number of dogs
bull No healthy dogs as a control
Future Directions
bull Evaluate the biological activity in patients with solid tumors
bull Compare the cytokine production after local treatment
lucasrodriguesestimavetbrACKNOWLEDGMENT
Mirtes MartisLarissa LosowskiDenise SamiaKaique BrazAna Carolina FariaDaiana SousaFelipe FernandesGraziela SantosElena ToazzaElis MontiCarolina FabriLarissa LopesGiza CabralKladine MoniqueSthefany Chagas
Joyce Ana Paula KarenBarbara Michele CharlesAline Andrade - Gisele Paim
lucasrodriguesestimavetbrACKNOWLEDGMENT
Mirtes MartisLarissa LosowskiDenise SamiaKaique BrazAna Carolina FariaDaiana SousaFelipe FernandesGraziela SantosElena ToazzaElis MontiCarolina FabriLarissa LopesGiza CabralKladine MoniqueSthefany Chagas
Joyce Ana Paula KarenBarbara Michele CharlesAline Andrade - Gisele Paim
