AACR in the news

Cancer vaccines are getting some news from the ongoing AACR meeting in Los Angeles. Most of the news in the media is about the HPV vaccine to prevent cervical cancer. However, the cervical cancer vaccines are really only vaccines against the virus that causes cervical cancer, and so are more like other microbio vaccines, e.g. flu vaccines. To call them cancer vaccines is a bit of a misnomer, and also trivializes the much more difficult issue of making true cancer vaccines, i.e. vaccines that can effectively discriminate cancerous from noncancerous cells and can overcome self tolerance.

The most interesting developments in cancer vaccines are in Dendreon's Provenge for prostate cancer. This is a vaccine against prostatic acid phosphatase, and is basically designed for the immune system to mop up any residual prostate cells after prostatectomy. Provenge is awaiting final clearance from the FDA for marketing in advanced prostate cancer (hormone-refractory prostate cancer, HRPC); it got a very favorable advisory panel review in late March. Provenge is the most important cancer vaccine to discuss because it is the first to show efficacy in Phase III trials, will most likely be the first to be approved, and also is designed to target the most common cancer in men.

The way Provenge works is of general geeky interest and explains its relative effectiveness sans side effects versus other vaccine approaches. First, a patient's blood is drawn and the dendritic cells (the primary antigen-presenting cells of the immune system) are purified. These are then stimulated by a fusion protein of GM-CSF (a potent dendritic cell activator) and a prostatic acid phosphatase peptide. The cells are then reinfused back into the patient, where they will present the PAP epitope and costimulatory molecules to lymphocytes, inducing a specific immune response to PAP and overcoming the previously established tolerance to self antigens.

Provenge (aka Sipuleucel-T) is also being presented at AACR, with data showing the immune response to PAP can be boosted by repeated treatments in earlier stage prostate cancer (hormone-dependent prostate cancer, or HRPC). About 1 in 6 men will get some form of prostate cancer if they live to age 80. If it weren't for smoking, prostate cancer would be the number one cause of cancer deaths among men. (A similar situation exists for breast cancer in women.)