Washington: According to a study, a novel medication called enoblituzumab, a monoclonal antibody, is safe in men with aggressive prostate cancer and may promote clinical action against cancer across the body.
Researchers from the Bloomberg Kimmel Institute for Cancer Immunotherapy and the Johns Hopkins Kimmel Cancer Center are leading the phase 2 study. Enoblituzumab has the potential to be the first effective antibody-based immunotherapy treatment for prostate cancer if results from subsequent studies are positive. In a clinical trial, 32 men with high-risk or very high-risk prostate cancers who were scheduled for prostate cancer surgery were treated with six weekly infusions of enoblituzumab prior to surgery, and were followed for an average of 30 months thereafter. 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.
A description of the work was published in the journal 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 the first one that may have a role for prostate cancer, says lead study author and cancer immunology researcher Eugene Shenderov, M.D., Ph.D., assistant professor of oncology at the Johns Hopkins University School of Medicine.
Other existing antibody-based immunotherapy drugs have targeted immune checkpoints, natural on/off switches mediating immune responses, such as CTLA-4, PD-1 and LAG-3. Cancer cells hijack these checkpoints, turning off the immune response to cancer. “Drugs that block these checkpoints have had success in other types of cancers, including lung cancer and melanoma, but not in prostate cancer,” said Shenderov.
Enoblituzumab works by binding to a protein called B7-H3 that is overexpressed on prostate cancer cells and believed to impede the immune system’s ability to attack cancer cells. The new therapy could pack a one-two punch against cancer, Shenderov says, by blocking B7-H3’s inhibition of the immune system’s recognition and elimination of cancer cells, and also triggering a process called antibody-dependent cellular cytoxicity (ADCC), which leads to tumour 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,” Shenderov says. “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.”
The median age of study participants was 64 (age range 48-74). About half (47%) had a PSA greater than 10 ng/mL at diagnosis, which is abnormally high, and 50% had Gleason grade group 5 at biopsy, meaning they had highly aggressive disease. Patients were enrolled from February 2017 through June 2019. Enoblituzumab was confirmed to penetrate into prostate tumours and to bind to B7-H3 in the vast majority of participants, according to prostate samples studied after surgery.