Tumor-Directed T Cells for HER2-Positive Sarcoma

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HER2-specific T cells can persist for 6 weeks without evident toxicities in patients with HER2-positive sarcoma.
HER2-specific T cells can persist for 6 weeks without evident toxicities in patients with HER2-positive sarcoma.

Human epidermal growth factor receptor 2 (HER2)-specific chimeric antigen receptor (CAR)-modified T cells can persist for 6 weeks without toxicities in patients with HER2-positive sarcoma, a new study published online early in the Journal of Clinical Oncology has shown.

Because patients with metastatic or recurrent sarcoma continue to have poor outcomes and adoptive therapy with tumor-directed T cells is becoming an increasingly attractive treatment option, researchers sought to evaluate this approach in patients with sarcoma.

For the phase I/II clinical study, researchers enrolled 19 patients with recurrent/refractory HER2-positive sarcoma. Patients received escalating doses (1 x 104/m2 to 1 x 108/m2) of HER2-CAR T cells.

Results showed that all infusions were well tolerated and no dose-limiting toxicities occurred. Researchers found that HER2-CAR T cells persisted for more 6 weeks in seven of nine evaluable patients who received greater than 1 x 106/m2 HER2-CAR T cells (P = 0.005). 

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Researchers also detected HER2-CAR T cells at the tumor sites of both of two patients examined. Of 17 evaluable patients, four achieved stable disease for 3 to 14 months and three of these patients had their tumor resected. The median overall survival was 10.3 months.

The authors conclude that future studies should combine HER2-CAR T cells with other immunomodulatory approaches to improve the expansion and persistence of the T cells.

Reference

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. 2015. [Epub ahead of print]. doi: 10.1200/JCO.2014.58.0225.

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