Cabozantinib Activates Innate Immune Response, Eliminating Prostate Cancer

Cabozantinib activated innate immunity and completely eradicated prostate cancer in a study using a mouse model.
Cabozantinib activated innate immunity and completely eradicated prostate cancer in a study using a mouse model.

A drug used to treat certain types of thyroid and kidney cancers also eliminated invasive prostate cancer in a mouse model, according to a recent study published in Cancer Discovery.1

The drug cabozantinib (Cometriq) causes prostate cancer cells to release CXCL12 and HMGB1 — chemical signals that recruit neutrophils to destroy the tumor. Within 48 to 72 hours, cabozantinib resulted in almost complete elimination of prostate cancer from mice with aggressive cancer.

"We saw dramatic antitumor responses," said the study's lead investigator, medical oncologist and physician-scientist Akash Patnaik, MD, PhD, assistant professor of medicine, director of the Developmental Therapeutics Laboratory, and attending physician within the Genitourinary Oncology Program at the University of Chicago Medicine. "We used a difficult-to-treat, aggressive prostate cancer mouse model. We were very surprised to see complete eradication of the most invasive, poorly differentiated tumors within days."

However, cabozantinib was less effective in a clinical trial of men with metastatic prostate cancer. These researchers believe they uncovered why many men in the clinical trial did not respond to treatment. The patients in that phase 3 trial had already received aggressive chemotherapy, and their immune systems may have been compromised, explained Patnaik.

Cabozantinib does not actually kill the tumor cells. Instead it causes the tumor cells to release factors that stimulate an immune system response. Many immunotherapy drugs activate the adaptive immune system (T-cells), whereas treatment with cabozantinib activates the innate immune system (neutrophils).

Based on their finding that cabozantinib can activate innate immunity overcoming an immunosuppressive tumor microenvironment, the researchers are planning clinical trials of cabozantinib and T-cell checkpoint immunotherapy combined on specific subtypes of advanced kidney and prostate cancers. “Our goal," Patnaik said, "is to enhance long-term anticancer responses from activating both innate and adaptive immunotherapy."

Reference

1. Patnaik A, Swanson KD, Csizmadia E, et al. Cabozantinib eradicates advanced murine prostate cancer by activating anti-tumor innate immunity. Cancer Discov. 2017 Mar 8. doi: 10.1158/2159-8290.CD-16-0778 [Epub ahead of print]
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