Researchers at Roswell Park Comprehensive Cancer Center in Buffalo have unveiled a promising advancement in cancer immunotherapy, introducing a novel approach that could significantly improve treatment outcomes for patients with solid tumors. The findings, published in the scientific journal *Cancer Cell* in October 2023, center on a new form of CAR T-cell therapy that incorporates the cytokine IL-36 gamma to enhance immune system activity within tumors.

This innovative therapy, developed under the leadership of Dr. Renier Brentjens, Deputy Director at Roswell Park, and research scientist Yihan Zuo, PhD, involves genetically modifying CAR T cells to express IL-36 gamma. These modified cells not only target cancer cells directly but also reprogram neutrophils—key immune cells often found in large numbers within solid tumors—to support an antitumor immune response. The approach addresses a longstanding challenge in oncology: the relative ineffectiveness of traditional CAR T-cell therapies against solid tumors, as compared to their success in treating blood cancers.

“Our findings reveal a new mechanism by which CAR T cells can activate other immune cells to fight solid tumors,” said Dr. Brentjens in a summary of the study’s conclusions. Zuo added that the research demonstrates how neutrophils, typically seen as obstacles in the tumor microenvironment, can be redirected to bolster the body’s attack on cancer.

Dr. Scott Abrams, who served as a co-senior author on the project, emphasized the broader implications of the work, noting that the study advances both scientific understanding and clinical approaches to treating solid tumors, which are often more resistant to immune-based therapies.

The research team collaborated with Dr. Christopher Hackett of Weill Cornell Medicine, and the study received financial support from the National Cancer Institute through grants U01CA256801 and P30CA016056. Building on these preclinical results, the team is now preparing to launch a clinical trial focused on patients with small cell lung cancer, a notoriously aggressive form of solid tumor.

As Roswell Park moves forward with clinical development, the study marks a significant step toward expanding the reach of CAR T-cell therapies beyond hematological malignancies. The trial will test whether the IL-36 gamma CAR T cells can achieve similar success in human patients as observed in laboratory models.

At present, the therapy remains in the research phase, with clinical trials expected to provide critical insights into its safety and effectiveness.