Monday, August 21, 2006

Cancer: Reducing tolerance of "self" tumors

CarbonBasedUnit writes "Many human tumor antigens are normal (not mutated) “self” proteins, so Rosenberg’s group treated melanoma (skin cancer) patients by immunizing with a melanocyte peptide while blocking CTLA-4, a protein that is thought to mediate immune self-tolerance. One patient was essentially cured and two improved while the other 11 patients showed no improvement. Nine of the 14 patients developed a remarkable variety of autoimmune complications, severe in 6, stopping the trial (all recovered). This paper also clearly establishes CTLA-4, an inducible protein expressed on activated T lymphocytes, as crucial in maintaining self tolerance in humans.
PubMed Entry" (originally posted on August 29, 2003)

Cancer regression and autoimmunity induced by cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma.
Phan GQ, Yang JC, Sherry RM, Hwu P, Topalian SL, Schwartzentruber DJ, Restifo NP, Haworth LR, Seipp CA, Freezer LJ, Morton KE, Mavroukakis SA, Duray PH, Steinberg SM, Allison JP, Davis TA, Rosenberg SA. PNAS 2003 Jul 8;100(14):8372-7

Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), also designated CD152
Regulatory T lymphocytes express CD4 and CD25 on their surface.

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