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Antibody-based immunotherapy shows promise in high-risk prostate cancer

Image credit – Johns Hopkins School of Medicine Media Relations

CANCER DIGEST – May 14, 2023 – In the first clinical trial of an antibody-based immunotherapy drug to show promise in men with advanced, high-risk prostate cancer, patients treated with enoblituzumab before surgery showed undetectable PSAs a year later, a new study shows.

In the phase 2 clinical trial led by Eugene Shenderov, MD, PhD of Johns Hopkins University School of Medicine, 32 men with high-risk prostate cancer were treated with enoblituzumab for six weeks before surgery. After an average of 30 months of follow-up, 21 men (66%) had undetectable prostate-specific antigen (PSA) 12 months after surgery, suggesting there was no residual cancer.

The trial aims to evaluate the safety and effectiveness of enoblituzumab, a new antibody therapy, when administered prior to surgery in patients with localized prostate cancer. Immunotherapy drugs fight cancer by affecting the immune system to better recognize and attack cancer cells. There are several types of immunotherapies including T cell therapy, checkpoint inhibitors, vaccines and monoclonal antibodies.

Enoblituzumab is a monoclonal antibody that works by latching onto a protein called B7-H3 that is overproduced by prostate tumors and is believed to blunt the immune system’s ability to recognize and attack the cancer cells. It is hoped that blocking B7-H3 will both open the tumor to immune system attack and also trigger a process called antibody-dependent cellular toxicity (ADCC).

This leads to tumor cell destruction by stimulating activation of other immune cells such as macrophages and natural killer cells that seek out and destroy cancer cells. For that reason researchers are hopeful that enoblituzumab will be effective against multiple types of cancer.

Shenderov explained that other antibody-based immunotherapy drugs target immune checkpoints, the on-off switches of the immune system, which are often turned off by cancer cells. “Drugs that block these checkpoints have had success in other types of cancers, Shenderov said in a press release, "including lung cancer and melanoma, but not in prostate cancer."

The study involved 32 participants ranging in age from 48-74, with an average age of 64. Of those, 47% had a PSA greater than 10 ng/ml, which is abnormally high, and a Gleason grade of 5 at biopsy, a marker for high-risk cancer.

Participants underwent six weekly infusions of enoblituzumab before undergoing surgery. They were then followed for an average of 30 months. Twenty-one patients (66%) had undetectable PSA levels 12 months after the surgery, suggesting no remaining cancer.

“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.”

Sources: Johns Hopkins School of Medicine press release and Nature Medicine

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