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Neoadjuvant Therapy and High-Risk Localized Prostate Cancer

Neoadjunct TherapyThe next step is a multicenter randomized, placebo-controlled trial of Enoblituzumab.

A protein called B7-H3, highly expressed on prostate cancer cells, has a detrimental effect on prostate cancer. As Hopkins scientists discovered several years ago, B7-H3 is associated with more rapid progression of prostate cancer after local treatment with surgery or radiation; it also suppresses the immune system’s ability to fight the disease. 

But they found a way to block B7-H3: a monoclonal antibody drug called Enoblituzumab. Previously, Discovery reported on a small clinical trial: scientists Eugene Shenderov, M.D., D.Phil., F.A.C.P., and Emmanuel Antonarakis, M.D., gave Enoblituzumab to men with high-risk localized prostate cancer before prostatectomy and compared the men’s biopsy samples with prostate tissue removed during surgery. Their results were promising: men treated with six weeks of Enoblituzumab showed greater immune activity in their tumor microenvironment. They also had a drop in their PSA levels and a decrease in their Gleason scores. Shenderov presented these results at the 2022 meeting of the American Society of Clinical Oncology (ASCO), and a paper is currently under review.

The next step is a multicenter, randomized, placebo-controlled trial, which Shenderov is planning with Mohamad Allaf, M.D., and colleagues.

In a related study, published in Cancer Shenderov and pathologist Tamara Lotan, M.D., determined that there is increased expression of B7-H3 in men of African ancestry. “This may be one factor that helps explain why the disease is more aggressive in Black men,” says Shenderov. This study was among the first to use genetic ancestry markers “to add to emerging evidence that prostate cancer in men of African ancestry may have a distinct biology associated with B7-H3 expression.

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