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Earlier in this blog, I attempted to explain the excitement surrounding the use of the checkpoint inhibitors and activated T-cells to fight cancer. Now the New York Times has done an excellent series on this approach which is worth reading, and no doubt more comprehensive and comprehensible than my effort. I encourage you to read it here.
For prostate cancer, there are both challenges and some early positive results that remain intriguing. An excellent review article published in April reviews the completed and ongoing efforts to harness the immune system in prostate cancer specifically. As the authors note, there have been variable results. One of the key challenges is to identify those patients who will benefit from the treatment and to date, using antibodies to stain the cancer cells that are making the PD-1 ligand that turns off the immune system has been challenging, since there are no accepted reproducible tests yet. Nevertheless, as demonstrated in this article, some patients do seem to have remarkable responses that offer real hope if the science continues to advance. If you read that abstract, pay attention to the issue of auto-immune side effects: “One had grade 2 myositis, one had grade 3 hypothyroidism, and one had grade 2 hypothyroidism. None of these patients had a response.” What this means is that the immune system was activated, but instead of attacking the prostate cancer, it attacked their muscle or thyroid, and apparently ignored the evil cancer cells. This has been a general problem in the entire field. Yet, in melanoma, where the greatest progress has been made, we are learning to walk the line between killing tumor cells and damaging the normal tissue with immune therapy.
My bias is that with continued progress in the vaccine field in prostate cancer (where we have one of the only vaccines approved for treating cancer, Sipuleucel-T), combining a vaccine with an immune booster type of treatment will ultimately provide the best results. Various trials of this sort are already underway.
Edited January, 2017: Another article just appeared in the JCO evaluating ipilimumab, the antibody that shuts down CTLA-4 T-cells (these are cells that suppress an immune response) in patients with metastatic, castrate resistant prostate cancer before they received chemotherapy. Although there was some hint of activity with a higher PSA response (23% vs 8% with placebo) and slightly longer time to progression, the overall survival was not changed (28.7 months in 399 patients treated with ipilimumab vs. 29.7 months in 199 patients receiving placebo). I’m still awaiting a larger trial like this with an immune checkpoint treatment combined with a vaccine. One such trial started in August 2016 at UCSF. A similar trial with promising results was published 4 years ago by the NCI group. Progress…but slower than we would like.