SAN FRANCISCO, CA USA (UroToday.com) - Charles Drake, MD, PhD reviewed the already approved immunotherapies for prostate cancer and highlighted the other immunotherapies in development.
Sipuleucel-T (PROVENGE) is an FDA-approved autologous cell-based vaccine approved for metastatic prostate cancer. A retrospective analysis of the phase III trial demonstrated that patients with a lower PSA at the start of immunotherapy had a longer overall survival. Dr. Drake hypothesized that this result may be due to increased immune tolerance attributable to high circulating levels of PSA, rather than to PSA as a marker of disease burden. He cited that immunizing patients with proteins alone causes immune tolerance, not immunity. Reviewing the same data, he showed patients that had antigen spread (immunization to off-target antigens), after receiving the autologous transplant, also had a better survival.
Dr. Drake highlighted the developing immunotherapies including PROSTVAC-VF, GVax, and Listeria-based vectors. PROSTVAC-VF uses a vaccinia virus to immunize against PSA. It also contains immune co-stimulatory molecules to increase intigenicity. This is currently under phase II trial. GVax uses tumor cells which are transduced with GM-CSF, radiated, and then given back to the patient to induce an immune response. He mentioned a 32-patient randomized trial that is currently underway in which the treatment arm had GVax + radical prostatectomy. The results have not matured yet. The most interesting vector he presented was the Listeria-based vaccine. This bacteria typically causes food poisoning, but has been attenuated by deletion of a gene which prevents the bacteria from overtaking the cell and lysing it. Listeria is an intracellular organism, so if it becomes immunogenic, it will be via the class I antigen presentation pathway. This results in CD8 cell-based immunity. The vector contains 4 antigens and costimulatory molecules. In mice, both with and without cancer, Listeria was the most immunogenic compared to GVax and PROSTVAC-VF. This model has been used in a phase II pancreatic cancer study that showed an overall survival advantage. Dr. Drake mentioned that in the use of immune checkpoint inhibitors, in the previously published nivolumab and ipilimumab trials, neither prostate cancer nor rectal cancer patients responded. He suggested that the reason they may not have worked is that most prostate cancers do not seem to express PD-1, which is in part how tumors stimulate immune tolerance.
Highlights of a presentation by Charles Drake, MD, PhD at the 2014 Genitourinary Cancers Symposium - January 30 - February 1, 2014 - San Francisco Marriott Marquis - San Francisco, California USA
Johns Hopkins University School of Medicine, Baltimore, MD USA
Written by Philip Abbosh, MD, PhD, medical writer for UroToday.com
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