First evaluation of HER2-specific ‘killer’ T cells in humans
A clinical trial resulting from a decade of lab research has shown promise for a new type of immunotherapy treatment for patients with HER2-positive sarcoma (a tumor arising from bone and soft tissue) and may extend to other types of cancer, said researchers from the Center for Cell and Gene Therapy at Baylor College of Medicine, Texas Children’s Hospital and Houston Methodist Hospital and from Texas Children’s Cancer and Hematology Centers. Their report appears in the current issue of the Journal of Clinical Oncology.
“More than a decade ago, we devised a genetic approach to generate immune cells, called T cells, that are specific for HER2, an antigen (or protein) present on a broad range of cancers including breast cancer, sarcomas and brain tumors,” said Dr. Nabil Ahmed, associate professor of pediatrics at Baylor and a co-author of the study. “The approach relies on isolating T cells from cancer patients, growing them in the laboratory and genetically modifying them with HER2-specific chimeric antigen receptors (HER2-CARs). These HER2-CAR T cells are then infused back into patients and ‘seek out’ HER2-positive tumor cells and destroy them.”
Taking their research from the lab to the clinic, Ahmed and Dr. Stephen Gottschalk, professor of pediatrics at Baylor and co-author of the study, and their team embarked on a clinical study to establish the safety of their therapeutic approach. The study included 19 pediatric and adult patients with HER2-positive sarcoma who had failed conventional therapies. They received increasing doses of HER2-CAR T cells. Infusions of HER2-CAR T cells were well tolerated, and T cells ‘homed’ to tumor sites. Several patients had clinical benefit, and eight patients survived for more than one year after T cell infusion.
“Using T cells as immunotherapy for cancer is increasingly being explored over the last 10 to 15 years,” said Gottschalk. “But there have not been too many CAR T-cell therapy studies for solid tumors so far, particularly for cancers that express HER2. We’ve now shown that indeed HER2-CAR T cells are safe up to the highest dose level tested, and since HER2 is expressed in a broad range of cancers, we are hopeful that our approach can be further developed to benefit many patients.”
“If you look at the history of cancer therapy, there are few examples of ‘magic bullets’ that can cure cancer alone,” Gottschalk said. “In general, combining different agents has proven most effective, and now we can think about different ways to explore this using HER2-CAR T cells.”
Ahmed and Gottschalk also are members of Baylor’s NCI-designated Dan L Duncan Cancer Center. Others involved in the study included Vita Brawley, Meenakshi Hegde, Catherine Robertson, Alexia Ghazi, Claudia Gerken, Enli Liu, Olga Dakhova, Aidin Ashoori, Amanda Corder, Tara Gray, Meng-Fen Wu, Hao Liu, John Hicks, Nino Rainusso, Gianpietro Dotti, Zhuyong Mei, Bambi Grilley, Adrian Gee, Cliona Rooney, Malcolm Brenner, Helen Heslop, Lisa Wang, all of Baylor; Winfried Wells, of the Institute for Tumor Biology and Experimental Therapy, Frankfurt, Germany; and Peter Anderson, of The University of Texas MD Anderson Cancer Center.
The research was supported in part by the V Foundation for Cancer Research, the Cancer Prevention and Research Institute of Texas, Stand Up To Cancer St. Baldrick’s Pediatric Dream Team Translational Research Grant (SU2C-AACR-DT1113; Stand Up To Cancer is a program of the Entertainment Industry Foundation administered by the American Association for Cancer Research), the Hoag Foundation, the Alliance for Cancer Gene Therapy, Alex’s Lemonade Stand Foundation, the Clinical Research Center at Texas Children’s Hospital and the Dan L Duncan Institute for Clinical and Translational Research at Baylor College of Medicine.
Texas Children’s Cancer Center is a joint program of Baylor College of Medicine and Texas Children’s Hospital and is the pediatric program of the Duncan Cancer Center.