M Christina Cox

Ematologia M Christina Cox

Adapted from Greenlee et al. CA Cancer J 2001;51:15–36

Lymphoma A

nn

ual

incid

en

ce

Year

~4% year increase

60,000

45,000

30,000

15,000

0

1980 1985 1990 1995 2000

MC Cox, ISS 14 febbraio 2012

In Italy the 6° type of cancer for incidence rate

1)Aggressive NHL

- High proliferation

- Immediate Treatment

with curative intent

2) Indolent NHL

- Low proliferation

- Treatment can be

postpone

MC Cox, ISS 14 febbraio 2012

Overall Survival Progression free survival

Very responsive to Immunochemotherapy but …….

continuos relapse rate and progressively refractory to

further lines of therapies

Chemotherapy + passive Immunotherapy (Anti-CD20 MoAb Rituximab)

MC Cox, ISS 14 febbraio 2012

FLIPI2 score FLIPI score

1) Anti-Idiotype-Vaccine

several trials showing biological activity but up to now

uncertain clinical benefit

2) Dendritic-Cell-Vaccine

Only one trial:

MC Cox, ISS 14 febbraio 2012

Unique Id expression

Slow growing

Immune Responsive

18 patients relapsed after ≥1 treatment ( 4 patients after transplantation)

Experimental therapy: IL-4-DC-Vaccine s.c. (4 or more injections)

Overall Response Rate =33% (Complete Remission+Partial Remission)

Stable disease= 33%

Very long-lasting remission

MC Cox, ISS 14 febbraio 2012

Why no more

studies???

BLOOD, 1 JANUARY 2009 VOLUME 113, NUMBER 1

MC Cox, ISS 14 febbraio 2012

IgG1

Th-7-type immune response

IL-17

IFNγ

CD80 CD86 CD40 CD83 CD25 HLA-DR

IFN

-DC

IL

-4-D

C

CD123

MC Cox, ISS 14 febbraio 2012

IFN-DC, exhibit a phenotype of highly

active partially mature DC, endowed with

high migratory and immuno-stimulatory

activities, along with a strong capability

of inducing cross-priming of CD8+ T cells

MC Cox, ISS 14 febbraio 2012

MC Cox, ISS 14 febbraio 2012

NHL cells Heat shock g-radiation UVC

radiation

Trattamento con

cyclophosphamide

Espressione di:

Hsp70 Hsp90

CRT

HMGB1

Citochine infliammatorie

Analisi della

apoptosi/necrosi

IFN-DC NHL cells

Analisi della produzione di citochine

modulazione marcatori di membrana

Analisi dell’uptake e

intracellular trafficking/processing

Ottimizzazione

della procedura di

loading antigenico

ONGOING PRE-CLINICAL TRIAL

IFN-DC

Analisi della produzione di citochine

modulazione marcatori di membrana

Analisi dell’uptake e

intracellular trafficking/processing

Ottimizzazione

della procedura di

loading antigenico

Elispot (IFN-g, granzyme-B)

Analisi della risposta

Analisi della risposta

cellulare/citotossica

ONGOING PRE-CLINICAL TRIAL

Relapsed (>1 relapse)

Follicular Lymphoma

1)Biopsy of Lymph node

and FL cell isolation

2)Apheresis of CD14+

monocytes

3) In Vitro manipulation of

DC and FL cells

4) IFN-DC-vaccine s.c.

injection x ≥6 courses

+/ - CTX 5) Monitoring of specific

immune response

Toxicity & Activity

MC Cox, ISS 14 febbraio 2012

MC Cox, ISS 14 febbraio 2012

MC Cox, ISS 14 febbraio 2012

•M Antonietta Aloe-Spiriti

•Elena Cavalieri •Maria Christina Cox

Filippo Belardelli

Caterina Lapenta

Carmela Rozera

Stefano Maria Santini

Imerio Capone

Paola Rizza

Enrico Proietti

•Maria Concetta Petti

MC Cox, ISS 14 febbraio 2012