Unformatted text preview: mphocyte antigen 4 (CTLA-4) by
ipilimumab may increase activity of T effector anti-tumor cells.
Possible uses in:
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
• 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Anti CD52 + Anti- EGFR + Anti VEGF Mylotarg = Anti CD33 (myeloid marker) + calicheamicin (cytotoxin) withdrawn.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
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- Mutation, cells, tumor cells, Ways Tumor Cells