How ‘chemoimmunotherapy’ may help destroy advanced PCa

Recently published research on a novel chemotherapy-immunotherapy combination is “exciting for multiple reasons,” says one expert.

Use of a novel chemotherapy-immunotherapy combination achieved near complete remission in a study of mice with advanced prostate cancer that a leading expert said is “exciting for multiple reasons.”

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An international team, made up of researchers from the University of California, San Diego School of Medicine, as well as universities in Austria and Germany, appears to overcome the challenge of treating larger prostate tumors, which typically do not respond to chemotherapy. Larger prostate tumors accumulate cells that suppress immune response, allowing cancer to progress despite treatment, according to a UC San Diego press release.

Interestingly, prostate cancer doesn’t respond to checkpoint inhibitors, which can unleash the immune system to better fight the cancer. Prostate cancer’s resistance to these immunotherapy drugs could be due, in part, to immunosuppressive B cells, which are more likely to be found in advanced and metastatic cancers in humans and larger prostate tumors in mice.

To test what is called chemoimmunotherapy, the authors studied three advanced prostate cancer mouse models, all of which were resistant to low doses of oxaliplatin (Eloxatin), an immunogenic chemotherapeutic agent that has been shown to be effective in the treatment of aggressive prostate cancer.

When the authors blocked immunosuppressive B cells or removed them before oxaliplatin treatment, the prostate tumors were almost completely destroyed by the mice’s immune cells. The researchers obtained similar results when low-dose oxaliplatin was combined with a checkpoint inhibitor, according to the release.

“The presence of such B cells in human prostate cancer calls for clinical testing of this novel therapeutic approach,” said first author Shabnam Shalapour, PhD, of the University of California, San Diego.

Findings from the study were published in Nature (2015; 521:94-98).

NEXT: Dr. Thrasher's take on the study

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J. Brantley Thrasher, MD, of the University of Kansas in Kansas City, said the research “is exciting for multiple reasons.”

“First, we know that many tumors, over time, become resistant to our treatments. It’s interesting to me that the authors found that disabling certain immunosuppressive B cells allowed the chemotherapy to work more effectively at killing the tumors. This may hold great promise in treating advanced prostate cancer-a stage that has been resistant to many of our treatments, especially chemotherapy,” Dr. Thrasher said.

Chemoimmunotherapy may hold promise for the treatment of other cancers, as well, according to Dr. Thrasher, who is not an author on this study.

“Obviously, next steps would be human trials with this therapy, likely in advanced stages of the disease,” Dr. Thrasher said. “Many of these therapies are tested in late stages of the disease, when most other treatments have been exhausted and the experimental therapy would also be less effective. However, if it is found to be effective and tolerated in this group, it may have wide applicability.”