Shielding CAR T cells with IL-15 can increase performance against solid tumors

According to the researchers, CAR T cells have shown limited efficacy in patients with solid cancers, despite dramatic successes in some hematologic malignancies. Now, preclinical studies by scientists at Baylor College of Medicine and Texas Children’s Cancer Center show that adding IL-15, which supports T cell survival and proliferation, improves the performance of CAR T cell-based immunotherapies could.

The results will be published in Nature.

In the Phase I clinical trials discussed in NatureResearchers tested glypican-3 (GPC3)-specific CAR T cells that co-express IL-15 in adults with hepatocellular carcinoma (HCC) and children with GPC3-expressing solid tumors, including HCC. The first patient cohorts received only GPC3-CAR-T cells. The GPC3-CAR-T cells were found to be safe, with maximal cell expansion occurring two weeks after infusion; However, no objective antitumor responses were observed.

GPC3 CAR T cells armed with IL-15 were examined in the second patient cohort, which again included adults and children with GPC3-expressing solid tumors. Patients enrolled in these studies demonstrated significantly increased CAR T cell expansion, with 33% (4/12) of subjects showing an objective antitumor response and 66% (8/12) having stable disease for at least four weeks. Patients who received IL-15-equipped GPC3 CAR T cells had a higher incidence of cytokine release syndrome, but symptoms improved rapidly with additional medications.

“The results are encouraging and represent a major step forward in improving the effectiveness of CAR T cells in children and adults with solid tumors. The correlative studies from this study have provided unique insights into the development of tumor-infiltrating CAR-T cells and provided a roadmap for developing the next generation of more effective, less toxic cellular immunotherapies,” said corresponding author Andras Heczey, MD, associate professor of pediatrics – Hematology and Oncology at Baylor and Director of the Liver Tumor Program at Texas Children’s Cancer Center.

Scientists from the Dan L. Duncan Comprehensive Cancer Center, the Center for Cell and Gene Therapy, the Children’s Hospital of Philadelphia, the Perelman School of Medicine at the University of Pennsylvania, the University of Houston, St. Jude Children’s Research Hospital and Lineberger Comprehensive Cancer Center and the University of North Carolina also participated in the current study.

The study shows that IL-15 increases the expansion, intratumoral survival and antitumor activity of GPC3 CAR T cells in patients. The results highlight the potential of IL-15-modified CAR-T cells to improve treatment outcomes in solid tumors.