Jim Brooks, MD, and Carolyn Bertozzi, PhD, Awarded Stanford Cancer Institute’s (SCI) Innovation Grant for Prostate Cancer Research

Jim Brooks, MD and Nobel Laureate Carolyn Bertozzi, PhD, have been awarded one of the Stanford Cancer Institute’s (SCI) Innovation Awards for March 2025. Their project, titled “PSMA-Targeted Sialidase for Prostate Cancer Immunotherapy,” aims to redefine prostate cancer treatment by employing advanced immunotherapy techniques.

Dr. Brooks and Dr. Bertozzi’s collaboration builds on their December 2024 study, which identified critical findings into how prostate cancer cells evade detection by the immune system.

The Science Behind the Grant

In their earlier research, Dr. Brooks, Dr. Bertozzi, and their co-authors demonstrated how prostate cancer cells manipulate their surface sugars to avoid immune detection. The cancer cells were found to be cloaked in a sugar called sialic acid, which binds to Siglec receptors on immune cells, effectively turning off the immune response. This mechanism is similar to other immune checkpoints, such as PD1/PDL1, which are already targeted by successful cancer immunotherapies. Blocking the interaction between sialic acid and Siglec receptors in preclinical models led to significant tumor shrinkage, laying the foundation for their innovative approach.

A Bold New Approach to Prostate Cancer

With the support of the SCI’s Innovation Award, Dr. Brooks’s and Dr. Bertozzi’s laboratories are collaborating to develop a new therapeutic solution. The project focuses on creating a fusion drug that combines a PSMA-targeted antibody with a specialized enzyme called sialidase. This drug will selectively target prostate cancer cells via the PSMA antibody, delivering the sialidase enzyme directly to the tumor.

Once there, the enzyme will act like a "lawn mower," stripping away the sialic acid sugars from the cancer cell surface. Without these sugars, the immune cells will no longer be suppressed by Siglec receptor interactions, allowing them to remain active and attack the cancer cells. The team plans to evaluate this innovative therapeutic approach in both cell culture and animal models of prostate cancer.