Proof Of Concept Study Sets Stage For Human Trial
WISCONSINREPORT.COM (08/19/2015) – Combining an experimental DNA vaccine against prostate cancer, with a new type of immunotherapy drug, increased vaccine effectiveness in mice with prostate cancer, according to a new study by UW Carbone Cancer Center scientists. Dr. Douglas McNeel, the study’s lead author, said the “proof of concept study” sets the stage for a human trial of the combination therapy, which began this week when the first patient received the vaccine.
“We’ve been looking for ways to improve the immune response, and we’re hopeful that by combining the vaccine with a PD-1 inhibitor, we’ll increase the efficacy of the vaccine,’’ says McNeel, a medical oncologist who has been researching and testing vaccines against prostate cancer for more than a decade.
McNeel’s research is aimed at helping men whose prostate cancer recurs after initial treatment, as happens in about one third of cases. While physicians often treat this period when prostate specific antigen (PSA) levels are rising as a “watch and wait” period, McNeel’s lab has created a vaccine that trains the immune system’s T cells to look for prostate cancer cells that express prostatic acid phosphatase (PAP) and kill them. It does this by introducing a plasmid – a tiny piece of DNA that expresses PAP — training the immune system to recognize and destroy cells with this protein.
While the vaccines have been shown to be safe in human trials, they may not be as effective at killing cancer cells in patients with more advanced disease. The newest mouse trial shows why: As the T cells are trained to look for prostate cancer cells, they also begin to express more of a protein called Programmed Cell Death (PD1), which stops the immune system from attacking its own cells.
However, when the mice also received drugs that blocked either PD-1 on the T cell or the matching antigen PD-LI on the cancer cell, the anti-tumor response was much higher and in some mice, the tumors were completely eradicated.
In the human version of the trial, McNeel will combine a DNA vaccine called MVI-816 with a PD-1 blockade drug called pembrolizumab, to see if that can slow the growth of prostate cancer cells. The MVI-816 vaccine is made by Madison Vaccines Inc., a company which McNeel helped found. The company is supporting the trial, along with a grant from the Prostate Cancer Foundation.
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