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Immunotherapy

Immunotherapy. Ivo Minárik, 200 7. Immunotherapy 2. Suppress immune response Encourage immune response. Suppressing immune response. immunosuppresive drugs – e.g . Cyclosporin , tacrolimus , corticosteroids , etc . Antibodies Dendritic cells Regulatory T cells. Antibodies.

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Immunotherapy

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  1. Immunotherapy Ivo Minárik, 2007

  2. Immunotherapy 2 • Suppress immune response • Encourage immune response

  3. Suppressing immune response • immunosuppresivedrugs – e.g. Cyclosporin, tacrolimus, corticosteroids, etc. • Antibodies • Dendritic cells • Regulatory T cells

  4. Antibodies • Anti-lymphocyte globulin – depletionofallogeniclymphocytesbefore organ transplatation • Anti-CD3 – promising in DM1 • Anti-CD4 - disappointing

  5. Antibodies 2 • Anti-TNFαtherapy (infliximab) – rheumatoid arthritis • Receptor for TNFα • Receptor for IL-1 • Antibodies against adhesion molecules (natalizumab) – block migration of lymphocytes to the site of inflammation – Crohn‘s disease, multiple sclerosis

  6. Role ofcostimulatorymolecules

  7. Interference with costimulatory pathways • CTLA4Ig – binds to CD80 and CD86 • Psoriasis • Anti-CD40L – on surfaceof T cells

  8. Immune modulation • Manipulating T regulatorycells (IL-10, TGFβ), immature dendritic cells

  9. Dendritic cells • TLR receptors (Toll-like) – essentialfortheinitiationofimmune response • If no TLR costimulation – Tcellanergy, expansionofregulatory T cells

  10. Allergy • Hyposensitization – repeatedapplicationofgraduallygrowingdosesofallergen • Lastsfor 3-5 years • Isotypeswitch, degranulationof mast cells • Subcutaneous, inhalation, ingestion

  11. Encouraging immune response • Cancertherapy – nonspecific (IL-2, IFNa) × specific • Tumor cells – lowerexpressionof MHC I, productionof IL-10, TGFβ, VEGF, frequentmutations

  12. Antibodies • Ab+cytotoxicdrug/radioisotope/toxin – difficult to asignappropriate antigen fortargeting • Disappointing – antigen instability, inefficientkilling, inefficientpenetration • Especiallyusedforlymphomasandleukemias

  13. Antibodies 2 • Targetinggrowthfactors + othermolecules • Bevacizumab (VEGF) – coloncancer, renalcancer • rituximab (anti CD20) – non-Hodgkinglymphoma

  14. Strategy to enhance Tcell immunity • Antigens + adjuvant (GM-CSF, extract from Corynebac.parvum, CpG) • Dendritic cells – antigens in the form of peptide (HLA restriction),cDNA, RNA, necrotic or apoptotic cells • TILs (tumor infiltrating lymphocytes) • Adoptive cell transfer

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