Dr. Charles G. Drake: PCa Immunotherapy

Prostate Forum recently spoke with Dr. Charles G. Drake of the Johns Hopkins University of Medicine in Baltimore about immunotherapy for prostate cancer. You can read the entire interview, in which he discusses Provenge, Prost-VAC VF, Yervoy (Ipilimumab), PSMA, and GVAX, in Prostate Forum Volume 15 Number 7.

Prostate Forum asked: What do you think are the most exciting ideas in immunotherapy for prostate cancer today?

Dr. Drake said: “The immune checkpoint that has been tested in prostate cancer and has been around a little bit longer is CTLA-4. But there’s another immune checkpoint that is probably more important on the CD8 cells. These are the killer cells. The immune checkpoint is called PD1 or Program Death-1.

We found even in the Phase I trial we did at Hopkins and other places, that patients treated with an antibody that blocked PD1 had dramatic shrinkage of their tumors. We saw this in melanoma, which is not totally unexpected, and in kidney cancer, which is a little bit surprising. We even found it in lung cancer. PD1 blockage alone as a mono-therapy shrank tumors in those different cancers. Some of the patients who respond to PD1 do remarkably well. I have kidney patients in my own clinic who are many years out after completing treatment with a complete response by PET scan. It’s really a very exciting treatment for cancer.

In the next trial, called a Phase IB trial, we tested this in about 17 prostate cancer patients and, in fact, none of those patients showed their tumors to shrink like we saw in the lung cancer, melanoma or kidney cancer patients. That has dampened the enthusiasm a tiny bit because people say as a single agent it’s probably not going to work. But to my mind, we don’t treat most cancers with one thing at a time. We treat with combination chemotherapy or combinations of treatments.

Personally, I would really like to combine an active cancer vaccine like sipulceul-T, GVAX or ProstVac with PD1-blockade. And maybe even along with hormonal therapy at the same time. I think that is the place to go in the future. PD1 is an important immune checkpoint. I’ve really tried very hard to get PD1 to use in these clinical trials, but the problem is that it’s already in Phase III trials for a number of other cancers. It’s been frustratingly difficult to get the drug to try in combination trials for prostate cancer patients.

One of my good friends, Lawrence Fong at UCSF, finished a trial about a year ago that is reasonably similar to the one that we did. He tested the idea that if you vaccinated with Provenge you might end up seeing a nice T cell influx into the prostate gland. He has finished that trial and he has analyzed all the patients to see if T cells come into the prostate after vaccination. The difference between his trial and mine is that we had hormonal therapy built into our. He didn’t do that in his trial, but it’s an exciting clinical trial and I’m really waiting to see those results. If his data are positive, I think its really good evidence for the idea.”


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