A team of scientists based in Buffalo has made a significant advancement in cancer immunotherapy, developing a new type of CAR T-cell treatment designed to better combat solid tumors. The findings, published in the journal *Cancer Cell* in October 2023, mark a promising step forward in the ongoing effort to expand the effectiveness of CAR T-cell therapy beyond blood cancers.

Researchers at Roswell Park Comprehensive Cancer Center, in collaboration with Weill Cornell Medicine, engineered CAR T cells enhanced with IL-36 gamma, a molecule that boosts immune response. These modified cells—described as “armored”—are designed to reprogram neutrophils, a type of white blood cell, to support the immune system’s attack on solid tumors, which have historically been resistant to CAR T-cell therapy.

Dr. Renier Brentjens, Deputy Director at Roswell Park and a pioneer in CAR T-cell research, co-led the project. He explained that the innovation lies in the therapy’s ability to engage other immune cells within the tumor environment. “These IL-36 gamma CAR T cells not only target the cancer directly but also activate immune components like neutrophils to strengthen the antitumor response,” Brentjens noted.

Yihan Zuo, PhD, a research scientist on the team, emphasized the critical role of neutrophils in this new approach. According to Zuo, these cells, which often work to suppress immune activity in tumors, can be reprogrammed by IL-36 gamma to instead support the immune system’s cancer-fighting capabilities.

The breakthrough also sheds light on broader immune-tumor dynamics. Co-senior author Scott Abrams, PhD, highlighted the significance of the findings in understanding how different elements of the immune system interact within the tumor microenvironment. “This work provides new insights into how we can manipulate immune cells to work together more effectively against solid tumors,” Abrams said.

The research was supported by grants from the National Cancer Institute (U01CA256801 and P30CA016056) and lays the groundwork for the development of a clinical trial focused on small cell lung cancer, a particularly aggressive form of the disease. Dr. Christopher Hackett, MD, PhD, of Weill Cornell Medicine, also contributed to the study.

With the preclinical results now published, the research team is preparing for the next phase: bringing this therapy into clinical testing. The proposed trial will evaluate the safety and efficacy of IL-36 gamma armored CAR T cells in patients with small cell lung cancer.

As of now, the clinical trial is in development, and researchers continue to refine the treatment strategy in preparation for its next steps in human testing.