Dual Antigen Targeting by CAR T Cells Improves Immunotherapeutic Technique
Chimeric antigen receptor (CAR) T cells may have improved therapeutic potential when they have 2 targets, according to preclinical findings using a mouse model.1
CAR T cells are a promising immunotherapy approach to cancer treatment in which a patient's own immune cells attack tumors by targeting an identifying antigen that is displayed at high levels on cancerous cells. However, CAR T cells that target a single antigen have had mixed results in clinical trials, which may be due to ongoing variability in the antigens that tumors display.
This study, led by Nabil Ahmed, MD, at Baylor College of Medicine in Houston, Texas, demonstrated that CAR T cells engineered to target 2 tumor antigens were more effective at controlling tumors in an animal model than CAR T cells that target a single antigen. This construct targeted both HER2 and IL13Rα2. The antigen recognition domains were joined in tandem, and so the researchers dubbed it TanCAR. These targets were chosen because targeting them simultaneously was predicted to eliminate more than 90% of tumors in a cohort of 20 primary glioblastomas. Glioblastoma was described as epitomizing cellular heterogeneity.
In an animal model of glioblastoma, treatment with the dual-antigen CAR T cells led to antitumor activity over a longer period of time and improved survival compared to treatment with single-antigen CAR T cells. These findings suggest that engineering CAR T cells to target multiple antigens on tumor cells could result in immunotherapeutic approaches with better efficacy in treating some types of cancer.
In their conclusion, the researchers mentioned the safety concerns with CAR T cells, and they suggest that targeting 2 antigens could increase the risk to normal tissues.
1. Hegde M, Mukherjee M, Grada Z, et al. Tandem CAR T cells targeting HER2 and IL13Rα2 mitigate tumor antigen escape. J Clin Invest. 2016;126(8):3036-3052.