Researchers at Roswell Park Comprehensive Cancer Center in Buffalo have unveiled a promising new approach to treating solid tumors, a major challenge in cancer therapy. In findings published in the October 2023 issue of the journal *Cancer Cell*, the team introduced a novel form of CAR T-cell therapy, engineered with IL-36 gamma to enhance its effectiveness against solid tumors.

The study, led by Dr. Renier Brentjens, Deputy Director at Roswell Park, and co-authored by Yihan Zuo, PhD, and Scott Abrams, PhD, marks a significant step forward in the use of immunotherapy for cancers that have traditionally been resistant to such treatments. Unlike blood cancers, solid tumors have proven more difficult to target with CAR T-cell therapies due to their complex microenvironments and resistance mechanisms.

To address this, the research team developed CAR T cells “armored” with IL-36 gamma, a cytokine known to stimulate immune responses. These modified cells not only attack tumor cells directly, but also help reshape the tumor environment by reprogramming neutrophils—white blood cells that often suppress immune activity in tumors—to instead promote anti-tumor immunity.

Dr. Brentjens emphasized the potential of this new therapy to provide a viable option for patients with advanced solid tumors, a population with few effective treatment choices. Yihan Zuo, PhD, who played a key role in the research, highlighted the significance of neutrophil reprogramming in driving immune responses against tumors. Co-senior author Scott Abrams, PhD, noted that the work deepens scientists’ understanding of how immune cells interact with tumors, potentially opening new avenues for treatment.

The team collaborated with researchers from Weill Cornell Medicine, including Christopher Hackett, MD, PhD, to advance the development of this innovative treatment platform.

Encouraged by preclinical results, the researchers are now preparing for a clinical trial focused on small cell lung cancer, one of the most aggressive and difficult-to-treat solid tumors. This next phase of research is being supported by grants from the National Cancer Institute (NCI), specifically U01CA256801 and P30CA016056.

As preparations for the clinical trial move forward, the research team at Roswell Park continues to refine the IL-36 gamma CAR T-cell platform, aiming to bring a new therapeutic option to patients facing some of the most challenging forms of cancer.