A new study by researchers at the Johns Hopkins Kimmel Cancer Center and its Bloomberg~Kimmel Institute for Cancer Immunotherapy shows promise for a monoclonal antibody, enoblituzumab, as a safe and potentially effective immunotherapy agent against prostate cancer.
The drug is believed to have induced clinical activity against cancer in the body and was well-tolerated by the 32 men with high-risk or very high-risk prostate cancers who participated in the study.
Undetectable PSA Levels
Six weekly infusions of the drug before surgery led to 21 patients, or 66%, having undetectable PSA levels a year after surgery.
PSA refers to prostate-specific antigen, a protein made by cells in the prostate gland. PSA levels in the blood can be used as a marker for prostate cancer, as elevated levels of PSA may indicate the presence of cancerous cells in the prostate gland.
The drug works by binding to a protein called B7-H3 that is overexpressed on prostate cancer cells and impedes the immune system's ability to attack cancer cells.
This binding of enoblituzumab leads to blocking B7-H3's inhibition of the immune system's recognition and elimination of cancer cells, which in turn triggers antibody-dependent cellular cytotoxicity (ADCC).
According to the research team, this process leads to the destruction of tumor cells by activating additional immune cells, such as macrophages and natural killer cells.
The lead study author, Eugene Shenderov, a cancer immunology researcher and assistant professor of oncology at the Johns Hopkins University School of Medicine, stated that enoblituzumab could represent a new pathway for immunotherapy against multiple cancers, the first one that may have a role for prostate cancer.
According to the team, other existing antibody-based immunotherapy drugs have targeted immune checkpoints and 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. However, drugs that block these checkpoints have succeeded in other types of cancers, including lung cancer and melanoma but not prostate cancer.
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Prostate Samples
The median age of the trial participants was 64. Half had excessively high PSA levels at diagnosis (more than ten ng/mL), and 50% had Gleason grade group 5 illness (very aggressive disease) at biopsy.
According to prostate samples examined after surgery, enoblituzumab was proven to infiltrate prostate tumors and bind to B7-H3 in the majority of individuals.
Enoblituzumab's moderate side effects included weariness, neurological symptoms such as headaches or vertigo, and flu- or cold-like symptoms.
The study's findings need to be confirmed in bigger study cohorts because they are exploratory.
"However, these results in high-risk prostate cancer patients, and the broader need for immunotherapeutic strategies with efficacy in prostate cancers, provide justification to further develop multipronged approaches that include targeting B7-H3 to optimize antitumor activity in prostate cancers and other solid malignancies," said senior study author Emmanuel S. Antonarakis.
To evaluate the therapeutic activity of the medicine in comparison to existing standards of care, researchers are currently preparing a bigger, randomized trial of enoblituzumab in patients with recently diagnosed prostate cancer.
The study was published in the journal Nature Medicine.
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