ImmunomodulatorBy Dr.Supasek Sarachitti D.V.M.

What is Immunomodulator

Immunomodulator is a substance (e. g. a drug, cell ) which has an effect on the immune system.

There are two types of effects1 Immunostimulation2 Immunosuppression

Development Immunomodulator

• Modulating Immune System• Immunomodulators in clinical

development• Infectious Diseases• Cancers

CD56 Antigen : Natural Killer cells (NK cells)

- First in the line of defense against viral infections and solid tumors

- Induction of graft versus leukemia (GVL) effects without induce graft versus host disease

- Given as donor lymphocyte infusion (DLI)

NK cells are innate immune lymphocytes critical to host defense against invading infectious pathogens and malignant transformation through elaboration of cytokines and cytolytic activity

Human NK cells comprise approximately 10- 20% of all blood lymphocytes

Natural Killer Cell

About Interleukin II (IL-2)

Interleukin-2 (IL-2) is a protein that occurs naturally in your body and plays an important role in activating your immune system. The immune system protects the body from foreign substances, cells, and tissues by responding to and resisting diseases

Why not success?? Why must use from Haploidentical??

Cytotoxicity before and after stimulation with rhIL-2 at aneffector-to-target cell ratio of 50:1; two-factorial variance analysiswith repeated measures; median, Q1, Q3, minimum and maximum;mean effect group (tumor vs healthy control), mean effect time(before vs after stimulation), and interaction group × time: P<0.01

Cancer Immunol Immunother (2005) 54: 87–92

s.c. IL-2 increases NK cell effectors. The absolute NK cell(CD56/CD3) and T-cell (CD3) numbers were determined by multiplyingthe absolute lymphocyte count from the complete blood countwith the percentage of each respective cell type. Percentages weredetermined by flow cytometry from the lymphocyte gated window ofthe mononuclear cell population.

Trastuzumab and IL-2 in Breast Cancer; Tanya Repka; Clinical Cancer Research; Vol. 9, 2440–2446, July 2003

Why NK cells Transplant can decrease GVHD

The decrease in GVHD was explained by donor NK cell alloreactivity against host antigen presenting cells (dendritic cells) that prevents presentation of host antigens to donor graft T-cells

G. Suck / Seminars in Cancer Biology 16 (2006) 412–418

What is LTCILTCI = Lymphocyte T Cells Immunomodulator

- Single chain polypeptide- Purification of protein from bovine-derived

stromal cell- Bovine protein is homologous with other

mammalian species and is a homologous 50 kDa glycoprotein with an isoelectric point of 6.5

Mechanism of Action

• LTCI is a potent regulator of CD-4 lymphocyte production and function.

• LTCI will increase lymphocyte numbers and IL-2 production in animals

Indication

treatment of cats infected with FeLV and/or FIV, and the associated symptoms of lymphopenia, opportunistic infection, anemia, granulocytopenia, or thrombocytopenia

Thank you