Prostate Cancer Vaccines Getting Some Needed Attention

Back in 2010, the FDA approved the first prostate cancer vaccine, Provenge. Since then, several prostate cancer vaccines have been investigated in both preclinical and clinical settings.

These clinical studies include viral vectors, antigen-loaded dendritic cells, and DNA vaccines. Each clinical approach has its own set of advantages and disadvantages.

But, according to Gurkamal Chatta, MD, Clinical Chief at Roswell Park Cancer Institute, "Since 2010, there have been clinical studies of various immunotherapies for prostate cancer, but we really haven't had any other major improvements."

Cancer vaccines belong to a class of substances known as biological response modifiers. These modifiers work by stimulating or restoring the immune system’s ability to fight infections and disease.

There are two broad types of cancer vaccines:

• Preventive (or prophylactic) vaccines, which are intended to prevent cancer from developing in healthy people,
• Treatment (or therapeutic) vaccines, which are intended to treat an existing cancer by strengthening the body’s natural immune response against the cancer. Treatment vaccines are a form of immunotherapy.

Here is a quick summary of the three prostate cancer vaccines:

• Provenge

This vaccine, sipuleucel-T, is approved for use in men with metastatic prostate cancer. The vaccine is used to treat advanced prostate cancer that's no longer responding to hormone therapy but is causing few or no symptoms.

Provenge hasn’t been shown to stop prostate cancer from growing, but it seems to help men live an average of several months longer.

Provenge is designed for specific men to stimulate an immune response to prostatic acid phosphatase (PAP), an antigen that is found on most prostate cancer cells.

Unlike traditional vaccines, which boost the body’s immune system to help prevent infections, the Provenge vaccine boosts the immune system to help it attack prostate cancer cells.

To make Provenge, white blood cells are removed from your blood. The cells are then exposed to a protein from prostate cancer cells called prostatic acid phosphatase (PAP). These modified cells are inserted into the patient by infusion into a vein. The cells help your other immune system cells attack the prostate cancer.

Studies are now being done to see if this vaccine can help men with less advanced prostate cancer.

• MOR209/ES414

According to Gurkamal Chatta, MD, he and his colleagues are conducting a phase I clinical trial of an immunotherapy for men with metastatic prostate cancer that has progressed in spite of standard treatment.

Prostate cancer metastasis occurs when cells break away from the tumor in the prostate. The cancer cells can travel through the lymphatic system or the bloodstream to other areas of the body.

The clinical trial for MOR209/ES414, is for a special type of antibody that researchers hope will guide the patient's T cells—specific white blood cells that help the immune system fight disease—to seek out a molecule called PSMA, which is found in most prostate cancers.

The science behind this clinical trial is based on results of a similar immunotherapy called blinatumomab (Blincyto), which is now FDA-approved for the treatment of acute lymphoblastic leukemia.

"If you could have a treatment that specifically targets the cancer, without causing collateral damage, you could provide meaningful quality of life in a subset of patients who are sicker and less able to tolerate toxic chemotherapies," Dr. Chatta said.

• INO-5150

The immunotherapy INO-5150 has shown promise as a treatment for prostate cancer that returns after surgery, according to a Phase 1b clinical trial.

Inovio Pharmaceuticals’ cancer vaccine generated immune responses in 60 percent of patients with recurrent prostate cancer and delayed the progression of the disease, researchers said.

Researchers said INO-5150 triggered immune-system T-cell responses against two proteins associated with prostate cancer in 60 percent of men whose disease had returned.

The proteins, PSA and PSMA, are biomarkers of the cancer.

The therapy also delayed the progression of the cancer, as assessed through PSA doubling time — the amount of time it takes for PSA levels to double.

“Our study provides encouraging immunologic and clinical data that Inovio’s immunotherapy product can generate antigen-specific CD8+ killer T-cell responses in the blood and link such responses to PSA changes in prostate cancer patients,” Dr. Neil Shore, a prostate cancer specialist at Urologic Associates of North Carolina, said in a press release.

Key objectives of the Phase 1b trial (NCT02514213) were to determine the safety of INO-5150 alone or in combination with INO-9012 and patients’ ability to tolerate it.