Pittsburgh, Tuesday 23, June, 2026. — Researchers at th e University of Pittsburgh, UPMC Hillman Cancer Center and the National Cancer Institute report that combining CAR T cell immunotherapy with a targeted radiopharmaceutical significantly improved tumor regression in preclinical models of neuroblastoma, a rare and aggressive cancer that usually forms in nerve tissue outside the brain that primarily affects children. The findings were published in Cell Reports Medicine .
Compared to radiation therapy alone, the addition of CAR T increased tumor shrinking and complete response rates by 80% percent, suggesting the promise of combination treatment to improve cancer outcomes in the future.
“In this study we used CAR T cell therapies that have been tested in clinical trials at the National Cancer Institute for children with recurrent neuroblastoma,” said senior author Ravi Patel, M.D. Ph.D ., Director of Radiopharmaceutical Therapy in the Department of Radiation Oncology at UPMC Hillman Cancer Center. “However, current cellular therapy approaches have limited efficacy in solid tumors such as neuroblastoma. Our results may offer a way in to improve the therapeutic effect of these CAR T cell therapy in solid tumor cancers.”
CAR T cell therapy —where a patient's disease-fighting T cells are engineered to recognize and attack cancer—has transformed treatment for certain blood cancers but has shown limited success in solid tumors like neuroblastoma .
In this study, researchers paired CAR T with a systemically delivered radioactive drug [67Cu]Cu-LLP2A that targets a receptor expressed on tumor and immune cells called VLA-4. Once bound to its receptor target, the drug delivers localized radiation directly to the tumor and its surrounding microenvironment. Unlike conventional radiation, which is delivered from outside the body to a fixed location, radiopharmaceuticals circulate in the bloodstream and can reach cancer cells throughout the body, including metastatic sites.
The researchers found that the combination therapy worked through different mechanisms depending on the tumor’s sensitivity to radiation.
In radiation-sensitive tumors, the radiopharmaceutical directly damaged cancer cells and triggered an inflammatory response that effectively "primed" the tumor to respond better to CAR T cells.
However, in tumors resistant to radiation, the drug did not kill cancer cells directly. Instead, it reshaped the tumor microenvironment — the network of cells and molecules surrounding a tumor that can suppress immune attack — by reducing suppressive immune cells and allowing CAR T cells to enter. It converted what researchers describe as a "cold" tumor into a tumor more open to immune attack.
The combination outperformed each treatment alone, including complete tumor regression in a substantial portion of cases.
"That's the innovation that this paper presents," added Patel, "Radiopharmaceuticals have typically been used on their own and combinations are still being explored. Using them with CAR T cells is a new approach."
The research is preclinical, meaning it was tested in laboratory models rather than patients, and additional work is needed before it can move into human studies. Next steps include identifying biomarkers to help determine which patients are most likely to benefit, exploring how imaging could guide more precise treatment decisions, and establishing safe dosing and toxicity profiles.
The findings point to a potential new approach to one of the biggest challenges in solid tumor immunotherapy : helping CAR T cells penetrate and function within a suppressive tumor environment. If successful, this strategy could help expand CAR T beyond blood cancers and eventually offer new options for children with hard-to-treat disease.
Pitt co-authors of this research are Robert S. Edinger, Ph.D., George Diehl, Ph.D., and Hannah Khan, Ph.D.; additional co-authors are from the National Cancer Institute, National Institutes of Health, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, and the University of Missouri. Additional corresponding authors of the study are Freddy E. Escorcia, M.D., Ph.D., and Rosa Nguyen, Ph.D., of the National Cancer Institute.
This work was supported by the Center for Cancer Research (ZIA BC 012066 and ZIA BC 011800), National Institutes of Health (iCURE program and grants R01CA275766, K08CA241319, R01CA204018, and P30CA047904), and New Jersey Pediatric Hematology Oncology Research Center of Excellence.
Cell Reports Medicine
Animals
A radiopharmaceutical enhances CAR T cells against radio-sensitive and radio-resistant neuroblastoma by tumor sensitization and TME remodeling
23-Jun-2026
This work was supported by the Center for Cancer Research (ZIA BC 012066 and ZIA BC 011800), National Institutes of Health (iCURE program and grants R01CA275766, K08CA241319, R01CA204018, and P30CA047904), and New Jersey Pediatric Hematology Oncology Research Center of Excellence.