By fighting pathogens, specialized cells of our immune system help keep us healthy and free from infectious diseases. Immunotherapies teach these same cells to acknowledge and destroy cancer. The drugs have been remarkably successful in treating melanoma – a kind of skin cancer – in addition to lung, bladder, kidney and blood cancers. Only one type of immunotherapy, a kind of cancer vaccine, is currently approved for prostate cancer.
A brand new method
Researchers at City of Hope Hospital in Duarte, California, now report. Promising results With a unique approach called CAR-T cell therapy. It involves engineering immune cells called T cells once they are obtained from the patient's own body. The engineered cells are attached to proteins called chimeric antigen receptors (CARs) that bind to specific molecular targets (antigens) on cancer cells.
Once back within the body, the engineered CAR-T cells kill tumor cells that express their goal antigen. CAR-T cell therapies are currently only approved for blood cancers. Treatments may be highly effective against these diseases, but in addition they have difficult uncomfortable side effects, including in some cases a widespread inflammatory response referred to as cytokine release syndrome.
During their research, the researchers engineered CAR-T cells that specifically bind to a protein called prostate stem cell antigen (PSCA). PSCA is preferentially expressed at high levels in prostate tumors, especially during advanced stages of the disease and after the cancer has spread to bone.
The investigators treated 14 patients, all diagnosed with metastatic prostate cancer that was not responding to hormonal therapy. Each patient was treated with 100 million CAR-T cells either with or without additional treatment used to forestall the patient's other T cells from interfering with the anti-cancer attack. This second treatment is known as lymphodepletion.
What the study showed
The results were encouraging: In 4 patients, prostate-specific antigen (PSA) levels — which drop when prostate tumors shrink — dropped by 30% or more. One patient had a greater than 90 percent decrease in PSA throughout the 28-day statement period, together with shrinking cancer in his bones and soft tissues. This positive response lasted for eight months. Five patients had a gentle cytokine release syndrome that was effectively treated, and two patients experienced cystitis, an irritation of the bladder.
Unfortunately, CAR-T cells should not maintained at high levels after the surveillance period, and this may increasingly limit the effectiveness of the treatment. The team plans to explore strategies to extend the advantages of CAR-T in future research.
Prostate cancer is immunologically “cold,” meaning it’s well hidden from the immune system. Therefore, most immunotherapies have had limited success against prostate cancer. But CAR-T offers a more powerful technique to overcome a tumor's defenses, in accordance with Dr. Tanya Dorff, a medical oncologist at City of Hope and first creator of the study.
Observations
“It's a different and more profound treatment experience than hormonal therapy and even chemotherapy,” he says. Still, he says, the outcomes suggest that CAR-T therapy may emerge as a further immunotherapeutic option for men with prostate cancer.
“Because the CAR-T program uses a new and exciting way to kill cancer cells, more work will be needed to help understand both the mechanisms by which this happens, and as Dr. Einstein emphasizes, ways to reduce the side effects associated with new technology.”