US Pharm. 2023;48(6):4.
A new monoclonal antibody drug, enoblituzumab, is safe in men with aggressive prostate cancer and may induce clinical activity against cancer throughout the body, according to a phase II study led by investigators at the Johns Hopkins Kimmel Cancer Center and its Bloomberg-Kimmel Institute for Cancer Immunotherapy. If confirmed in additional studies, enoblituzumab could become the first promising antibody-based immunotherapy agent against prostate cancer.
In a clinical trial, 32 men with high-risk or very high–risk prostate cancers were treated with six weekly infusions of enoblituzumab prior to surgery and were followed for an average of 30 months. Twenty-one patients, or 66%, had an undetectable prostate-specific antigen (PSA) level 12 months following surgery, suggesting that there was no sign of residual disease. Additionally, the drug was well-tolerated overall; no patients had any surgical delays or medical complications during or after the operation. The work was published in Nature Medicine.
If enoblituzumab continues to perform well in further larger, randomized studies, it could represent a new pathway for immunotherapy against multiple cancers and be the first one that may have a role for prostate cancer, said lead study author and cancer immunology researcher Eugene Shenderov, MD, PhD, assistant professor of oncology at the Johns Hopkins University School of Medicine. Other existing antibody-based immunotherapy drugs have targeted immune checkpoints, such as CTLA-4, PD-1, and LAG-3. Cancer cells hijack these checkpoints, turning off the immune response. “Drugs that block these checkpoints have had success in other types of cancers, including lung cancer and melanoma, but not in prostate cancer,” said Dr. Shenderov.
Enoblituzumab works by binding to a protein called B7-H3 that is overexpressed on prostate cancer cells and is believed to impede the immune system’s ability to attack the cancer cells. The new therapy could block B7-H3’s inhibition of the immune system’s recognition and elimination of cancer cells, Dr. Shenderov said, adding that the drug might trigger a process called antibody-dependent cellular cytotoxicity, which leads to tumor cell destruction by activating additional immune cells, such as macrophages and natural killer cells.
“Enoblituzumab appears safe and seems to activate the immune system in a way that involves both T cells and myeloid cells,” he explained. “What this means is if these results can be replicated in a larger, randomized study, it opens the possibility that combining this therapy with local, curative-intent therapies like surgical prostate removal or radiation therapy would allow this drug to potentially kill micrometastatic disease hiding elsewhere in the body, and therefore prevent a significant number of men from experiencing recurring disease. That could be a paradigm shift in prostate cancer.”
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