Engineered CAR T Cells Deliver Tumor-Targeted IL-12, Shrinking Solid Tumors in Mice

The design tethers IL-12 to PD-L1 to confine potent immune activation to cancer sites.

Overview

In Nature Biomedical Engineering, USC Norris and City of Hope report CAR T cells that secrete an IL-12–PD-L1 blocker fusion protein.
In mouse models of ovarian and prostate cancer, the approach reduced tumor size with minimal systemic toxicity.
The PD-L1–guided fusion concentrates IL-12 where tumors upregulate PD-L1, enhancing T-cell penetration and reprogramming the microenvironment.
Studies are underway in pancreatic cancer with plans to evaluate colorectal and brain tumors, and the team aims to begin clinical trials within one to two years.
Funding came from the Prostate Cancer Foundation, the U.S. Department of Defense and the NIH, and authors disclosed related patents and financial relationships.