Persistence of HER2-Specific CAR T Cells in HER2-Positive Sarcoma


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CAR T Cells in HER2-Positive Sarcoma

This first evaluation of the safety and efficacy of HER2-CAR T cells in patients with cancer shows the cells can persist for 6 weeks without evident toxicities, setting the stage for studies that combine HER2-CAR T cells with other immunomodulatory approaches to enhance their expansion and persistence.

—Nabil Ahmed, MD, MSc, and colleagues

In a phase I/II study reported in the Journal of Clinical Oncology,1 Nabil Ahmed, MD, MSc, of Baylor College of Medicine, Houston, and colleagues, found that infusion of T cells expressing HER2-specific chimeric antigen receptor (CAR) with a CD28.ζ signaling domain (HER2-CAR T cells) could produce persistent CAR T cell levels for ≥ 6 weeks in patients with HER2-positive recurrent/refractory sarcoma.

In the study, 19 patients received escalating HER2-CAR T doses of 1×104/ m2 to 1×108/m2. Infusions were well tolerated, with no dose-limiting toxicities being observed. At doses of ≥ 1×105/m2, HER2-CAR T cells were detected by quantitative polymerase chain reaction at 3 hours after infusion in 14 of 16 patients. HER2-CAR T cells persisted for ≥ 6 weeks in 7 of 9 evaluable patients who received a dose > 1×106/m2  (P = .005).

HER2-CAR T cells were identified at tumor sites of each of two patients examined. Among 17 evaluable patients, 4 had stable disease for 12 weeks to 14 months. Three of these patients received no additional therapy and had residual tumor removed, with the tumor from one patient exhibiting ≥ 90% necrosis. At the time of analysis, all three patients remained in remission at 6 to 16 months with no further treatment. Median overall survival of all 19 patients receiving infusion was 10.3 months (range = 5.1–29.1 months).

The investigators concluded: “This first evaluation of the safety and efficacy of HER2-CAR T cells in patients with cancer shows the cells can persist for 6 weeks without evident toxicities, setting the stage for studies that combine HER2-CAR T cells with other immunomodulatory approaches to enhance their expansion and persistence.”

Stephen Gottschalk, MD, of Baylor College of Medicine is the corresponding author for the Journal of Clinical ­Oncology article. 

Disclosure: The study was supported by the V Foundation for Cancer Research, Cancer Prevention and Research Institute of Texas, Hoag Foundation, Alliance for Cancer Gene Therapy, Alex’s Lemonade Stand Foundation for Childhood Cancer, Stand Up To Cancer St. Baldrick’s Pediatric Dream Team, Clinical Research Center at Texas Children’s Hospital, and Dan L. Duncan Institute for Clinical and Translational Research at Baylor College of Medicine. For full disclosures of the study authors, visit jco.ascopubs.org.

Reference

1. Ahmed N, Brawley VS, Hedge M, et al: Human epidermal growth factor receptor 2 (HER2)-specific chimeric antigen receptor–modified T cells for the immunotherapy of HER2-positive sarcoma. J Clin Oncol. March 23, 2015 (early release online).

 



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