Innovative CAR T Cell Technology Boosts Solid Tumor Cancer Treatment Potential

Chimeric antigen receptor (CAR) T cell therapy, which employs a patient's own immune cells to target and attack cancer, has revolutionized treatment for certain blood cancers like lymphoma. However, extending this success to solid tumors—including prostate, breast, lung, and ovarian cancers—has proven challenging, as these tumors create a hostile environment that hampers immune cell effectiveness.

Recent advancements come from a collaborative effort between the USC Norris Comprehensive Cancer Center and City of Hope. The team developed a groundbreaking approach where CAR T cells are engineered to produce a combined fusion of two key proteins: interleukin 12 (IL-12), a cytokine that activates immune responses, and a programmed death-ligand 1 (PD-L1) blocker, which inhibits a common immune checkpoint exploited by tumors to evade attack.

In preclinical studies involving mouse models of ovarian and prostate cancer, these modified CAR T cells effectively localized to tumor sites. They triggered a potent and localized immune response, significantly reducing tumor size without causing widespread toxicity. The IL-12 fusion protein was specifically delivered to the tumor by attaching to PD-L1 blockers, which naturally accumulate where tumors activate immune checkpoints, ensuring targeted and safe therapy.

This innovative approach enhances T cell penetration into tumors, transforms the tumor microenvironment to favor immune attack, and minimized adverse effects—a major hurdle in previous therapies. The findings, published in Nature Biomedical Engineering, suggest that this strategy could be applicable to other solid cancers, including gastrointestinal and brain tumors.

"By designing CAR T cells that release both IL-12 and a PD-L1 blocker locally, we can enhance their safety and efficacy, even against tumors resistant to conventional CAR T therapy," explained Saul Priceman, Ph.D., senior author and associate professor at USC. The team is optimistic that this method could be translated into clinical trials within one to two years.

Beyond prostate and ovarian cancers, the researchers are testing this approach in pancreatic, colorectal, and brain tumors. The broad potential of this technology lies in its ability to modify the tumor environment, making it more receptive to immune attack—a promising step toward expanding CAR T cell therapies to a wider range of cancers.

This development signifies a notable leap in solid tumor immunotherapy, representing a promising therapeutic avenue that could overcome previous limitations and substantially improve outcomes for many cancer patients.