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The NCI team also found that, in combination with chemotherapy, surgery, or T-cell transfer therapy, the effects of the GEMy treatment im proved. For example, giving mice a single dose of chemotherapy two days before the GEMy infu sion cured mice with rhabdomyosarcoma, mean ing the treatment completely eliminated all traces of cancer for more than 100 days. “I have never seen that kind of durable cure in my research before. Typically, cancer growth will slow down after treatment, but then it will come back with a vengeance,” Dr. Kaplan said. The team also found evidence that the chemo therapy and GEMys combination might prevent cancer from coming back. When the researchers reintroduced cancer cells into mice that had been cured by the combination treatment, tumors didn’t form. This suggests that the combination treatment leaves a long-lasting “immune memo ry” of the cancer, the researchers explained. As a final step in their study, the researchers cre ated GEMys from human cells grown in the lab. In lab dishes, the genetically engineered human cells produced IL-12 and activated cancer-killing immune cells. The team plans to test the safety of human GE

Mys in a clinical trial of adults with cancer and, if it proves to be safe, in children and adolescents with cancer. There are many unanswered ques tions they hope to explore, including whether the homing pattern of GEMys is similar in humans and mice, and whether IL-12 from the GEMys will cause side effects in patients. But the researchers are reassured by several fac tors. “We are delivering a small amount of IL-12 that’s similar to the body’s natural response to an infection, creating a ripple effect of immune ac tivation against the cancer. In addition, GEMys don’t multiply rapidly inside the body, so they’re not flooding the system with IL-12,” explained Sabina Kaczanowska, Ph.D., first author of the study. These are important considerations be cause high levels of IL-12 throughout the body can be toxic. “Although there are challenges of planning a first-in-human trial of a cell therapy, I’m grateful to have access to the resources of the NIH Clin ical Center and to be able to lean on the experi ence of my NCI colleagues who have had decades of experience developing cell therapies for can cer,” Dr. Kaplan added. Credit: National Cancer Institute

About the Center for Cancer Research (CCR): CCR comprises nearly 250 teams conducting ba sic, translational, and clinical research in the NCI intramural program—an environment support ing innovative science aimed at improving hu man health. CCR’s clinical program is housed at the NIH Clinical Center—the world’s largest hos pital dedicated to clinical research. For more in formation about CCR and its programs, visit ccr. cancer.gov. About the National Cancer Institute (NCI): NCI leads the National Cancer Program and NIH’s efforts to dramatically reduce the prevalence of cancer and improve the lives of cancer patients and their families, through research into preven tion and cancer biology, the development of new interventions, and the training and mentoring of new researchers. For more information about cancer, please visit the NCI website at cancer. gov or call NCI’s contact center, the Cancer Infor mation Service, at 1-800-4-CANCER (1-800-422 6237). About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, in cludes 27 Institutes and Centers and is a compo nent of the U.S. Department of Health and Hu man Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigat ing the causes, treatments, and cures for both common and rare diseases. For more informa tion about NIH and its programs, visit nih.gov.

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