Tregs blocking of cytotoxic t lymphocyte antigen 4

Info iconThis preview shows page 1. Sign up to view the full content.

View Full Document Right Arrow Icon
This is the end of the preview. Sign up to access the rest of the document.

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CD20 Anti HER2/neu Anti CD52 + Anti- EGFR + Anti VEGF Mylotarg = Anti CD33 (myeloid marker) + calicheamicin (cytotoxin) withdrawn.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...
View Full Document

This document was uploaded on 03/10/2014 for the course BIOLOGY 104 at Tufts.

Ask a homework question - tutors are online