Penn researchers are advancing cancer immunotherapy with armored CAR T cells that secrete interleukin-18, achieving strong response rates in a first-in-human study of patients who had exhausted other therapies.

The pivotal findings were published in the New England Journal of Medicine, marking a turning point for cancer immunotherapy despite initial funding challenges and limited resources.

Early trials began with treating chronic lymphocytic leukemia patients in 2010, showing promising responses that helped propel broader attention and eventual FDA approval of CAR T therapy in 2017.

Key researchers Carl June and Bruce Levine shifted from HIV/T cell work to cancer CAR T-cell therapy at the University of Pennsylvania in 1999, paving the way for early cancer trials.

The armored CAR T approach seeks to boost performance in both liquid cancers and solid tumors by addressing tumor microenvironment, durability, and cost.

This article is the first of a two‑part series tracing Penn’s CAR T-cell research from its early experiments to cutting-edge trials.

Broader goals include developing in vivo and allogeneic CAR T cells to speed up and simplify treatments, while exploring new targets and generations of CAR T cells to expand accessibility.

A 2025 study reported response rates above 80% in heavily pretreated patients using armored CAR T cells, indicating potential to overcome resistance to standard CAR T therapies.