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Tregs blocking of cytotoxic t lymphocyte antigen 4

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Unformatted text preview: mphocyte antigen 4 (CTLA-4) by ipilimumab may increase activity of T effector anti-tumor cells. Possible uses in: Prostate Cancers Lung Cancers Melanoma (approved for this use by FDA on March 25, 2011) Side Effects- Autoimmunity especially in GI tract How ipilimumab may work: Cytotoxic T cells express CTLA-4When CTLA-4 binds to B7 on dendritic cells, the cytotoxic T cells are inactivated. Therefore blocking of CTLA-4, should increase the activity of the cytotoxic T cells Regulatory T cells (these cells may decrease the activity of cytotoxic and helper T cells) also express CTLA-4. Blocking CTLA-4 on regulatory T cells may prevent these cells from blocking the activity of effector T cells (i.e. inhibit an inhibitor). skip * Study Overview •  The authors treated 676 patients with metastatic melanoma with an antibody to CTLA-4 (ipilimumab), the antibody plus a gp100 vaccine, or the vaccine alone. •  Patients who received ipilimumab with or without gp100 vaccine survived nearly 4 months longer than did those who received the gp100 vaccine alone. •  Adverse immune-related events were noted and some were severe, but most were reversible with appropriate treatment. Hodi et al; New Eng J Med 363 (8): 711-723 2010 binds to the ligand on the Dentritic cell and blocks the Tcell from apoptosis. Topalian et al, NEJM 2443-2454; 366; 2012 Safety, Activity and Immune Correlates of Anti-PD-1 Antibody in Cancer PD-1 is a receptor (found on T cells) for PD-L1 ligand (found on DCs). skip Topalian et al, NEJM 2443-2454; 366; 2012 receptors are blocked. Topalian et al, NEJM 2443-2454; 366; 2012 + + Anti CD20 Anti HER2/neu Anti CD52 + Anti- EGFR + Anti VEGF Mylotarg = Anti CD33 (myeloid marker) + calicheamicin (cytotoxin) withdrawn. Zevalin = Anti CD 20 + a chelator with indium-111 or yttrium-90 Tositumomab = Anti CD20 + I131 end of slide * Microspheres- carry antitumor molecules and can be injected directly into tumor. The microspheres then get stuck or “embolize” in tumor circulation creating a high dose of drug in the tumor. You can load the microspheres wi...
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