Tandem CAR T cells targeting HER2 and IL13Rα2 mitigate tumor antigen escape

Hegde, Meenakshi; Mukherjee, Malini; Grada, Zakaria; Pignata, Antonella; Landi, Daniel; Navai, Shoba A.; Wakefield, Amanda; Fousek, Kristen; Bielamowicz, Kevin; Chow, Kevin; Brawley, Vita S.; Byrd, Tiara; Krebs, Simone; Gottschalk, Stephen; Wels, Winfried S.; Baker, Matthew L.; Dotti, Gianpietro; Mamonkin, Maksim; Brenner, Malcolm K.; Orange, Jordan S.; Ahmed, Nabil

doi:10.1172/jci83416

Cited by 516 publications

(301 citation statements)

References 47 publications

(69 reference statements)

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“…Encouragingly, the TanCAR effectively redirected T cells to the two antigens and enhanced the function of CAR-T cells and the secretion of cytokines in vitro and in vivo. Therefore, the TanCAR-T cell agents were considered as a potential therapeutic method to control tumor growth as this study reported [74, 75]. Recently, a group combined bispecific antibody αHER2/CD3 and CAR-T therapy.…”

Section: Target Antigen Expressing On Solid Tumor Cell Surfacementioning

confidence: 99%

Chimeric antigen receptor T cells: a novel therapy for solid tumors

et al. 2017

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The chimeric antigen receptor T (CAR-T) cell therapy is a newly developed adoptive antitumor treatment. Theoretically, CAR-T cells can specifically localize and eliminate tumor cells by interacting with the tumor-associated antigens (TAAs) expressing on tumor cell surface. Current studies demonstrated that various TAAs could act as target antigens for CAR-T cells, for instance, the type III variant epidermal growth factor receptor (EGFRvIII) was considered as an ideal target for its aberrant expression on the cell surface of several tumor types. CAR-T cell therapy has achieved gratifying breakthrough in hematological malignancies and promising outcome in solid tumor as showed in various clinical trials. The third generation of CAR-T demonstrates increased antitumor cytotoxicity and persistence through modification of CAR structure. In this review, we summarized the preclinical and clinical progress of CAR-T cells targeting EGFR, human epidermal growth factor receptor 2 (HER2), and mesothelin (MSLN), as well as the challenges for CAR-T cell therapy.

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Section: Target Antigen Expressing On Solid Tumor Cell Surfacementioning

confidence: 99%

Chimeric antigen receptor T cells: a novel therapy for solid tumors

et al. 2017

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“…T cells expressing both CARs improved the antitumor response compared to pooled T cells expressing HER2 CARs or IL13Rα2 CARs. The same group generated a tandem CAR recognizing HER2 and IL13Rα2 simultaneously by inducing heterodimerization of the two targets (Hegde et al, 2016). This tandem CAR (tanCAR) further reduced antigen escape and had increased antitumor efficacy in pre-clinical models.…”

Section: Specificity and Safety Of Car T Cell Therapymentioning

confidence: 99%

Development of CAR T cells designed to improve antitumor efficacy and safety

Jaspers

Brentjens

2017

Pharmacology & Therapeutics

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Chimeric antigen receptor (CAR) T cell therapy has shown promising efficacy against hematologic malignancies. Antitumor activity of CAR T cells, however, needs to be improved to increase therapeutic efficacy in both hematologic and solid cancers. Limitations to overcome are ‘on-target, off-tumor’ toxicity, antigen escape, short CAR T cell persistence, little expansion, trafficking to the tumor and inhibition of T cell activity by an inhibitory tumor microenvironment. Here we will discuss how optimizing the design of CAR T cells through genetic engineering addresses these limitations and improves the antitumor efficacy of CAR T cell therapy in pre-clinical models.

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“…In order to overcome antigen escape risk and inter-patient variability, CARs co-targeting two or even three antigens are being developed in several solid malignancies, including breast, pancreatic and brain tumors (110)(111)(112)(113). Conversely, other investigators are testing dual constructs requiring both targets to be expressed on tumor cells in order to exert their cytotoxic activity (114) and inhibitory CARs able to redirect T cells activity from healthy tissues (115), with the aim of increasing CAR specificity and of preventing off-tumor side effects.…”

Section: Car T Cells For Solid Tumorsmentioning

confidence: 99%

Adoptive immunotherapy with CAR modified T cells in cancer current landscape and future perspectives

Coscia¹

2019

Front Biosci

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Tandem CAR T cells targeting HER2 and IL13Rα2 mitigate tumor antigen escape

Cited by 516 publications

References 47 publications

Chimeric antigen receptor T cells: a novel therapy for solid tumors

Chimeric antigen receptor T cells: a novel therapy for solid tumors

Development of CAR T cells designed to improve antitumor efficacy and safety

Adoptive immunotherapy with CAR modified T cells in cancer current landscape and future perspectives

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