Replies to post #4701 on Biotech Values

[urche]

Interesting twist on CTL-4 blockade:

I picked up this iceberg post from Yahoo where it had been plagiarized from SI, so I do so unabashedly on Ihub. This adds validity to the claim that CTL-4 blockade is an effective immunomodulatory strategy. Whether this is good or bad for MEDX, Pfizer, and now BMY, all of whom now are heavily invested in CTL-4 pipeline work, I am not sure. On the one hand, here is evidence that even in the eye, which is relatively spared from auto-immune pathology, there is evidence that the vaccine has effect. OTOH, this is probably going to be an increasingly vexing trend for drugs such as MEDX-010. I predict we will see a lot of "side-effects" caused by the immunomodulation gone amuck. This is not unexpected. We have had to deal with risk of infection during high dose steroid therapy for years. Similarly, some of the oncology drugs also appear to be causing increased incidence of secondary tumors---presumably by impairing the body's ability to detect or destroy de novo cancer cells.

Cytotoxic T Lymphocyte-Associated Antigen 4 Blockade in Patients with Metastatic Melanoma: A New Cause of Uveitis.

J Immunother. 2004 Nov;27(6):478-479.

Robinson MR, Chan CC, Yang JC, Rubin BI, Gracia GJ, Sen HN, Csaky KG, Rosenberg SA.

From the *National Eye Institute, National Institutes of Health, Bethesda, Maryland; and daggerSurgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.

Cytotoxic T Lymphocyte-associated antigen 4 (CTLA-4) is an important costimultory receptor expressed on activated T cells. CTLA-4 blockade using a monoclonal antibody (mAb) in conjunction with tumor vaccines has improved tumor responses in animal models and enhanced numerous models of T cell-associated autoimmune diseases. Two patients with stage IV metastatic melanoma vaccinated with the gp 100 melanocyte/melanoma differentiation antigen either before or during anti-CTLA-4 mAb therapy developed uveitis. This is the first report of autoimmune disease involving the eye in patients treated with anti-CTLA-4 mAb. This suggests that CTLA-4 is an important regulatory molecule for maintenance of tolerance to melanosomal antigens and prevention of uveitis.