The Role of Immunological Synapse in Predicting the Efficacy of Chimeric Antigen Receptor (CAR) Immunotherapy
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(2020) 18:134
REVIEW
Open Access
The Role of Immunological Synapse in Predicting the Efficacy of Chimeric Antigen Receptor (CAR) Immunotherapy Dongfang Liu1,2* , Saiaditya Badeti1, Gianpietro Dotti3, Jie-gen Jiang1, He Wang1, James Dermody4, Patricia Soteropoulos4, Deanna Streck4, Raymond B. Birge5 and Chen Liu1,6
Abstract Chimeric Antigen Receptor (CAR) immunotherapy utilizes genetically-engineered immune cells that express a unique cell surface receptor that combines tumor antigen specificity with immune cell activation. In recent clinical trials, the adoptive transfer of CAR-modified immune cells (including CAR-T and CAR-NK cells) into patients has been remarkably successful in treating multiple refractory blood cancers. To improve safety and efficacy, and expand potential applicability to other cancer types, CARs with different target specificities and sequence modifications are being developed and tested by many laboratories. Despite the overall progress in CAR immunotherapy, conventional tools to design and evaluate the efficacy and safety of CAR immunotherapies can be inaccurate, time-consuming, costly, and labor-intensive. Furthermore, existing tools cannot always determine how responsive individual patients will be to a particular CAR immunotherapy. Recent work in our laboratory suggests that the quality of the immunological synapse (IS) can accurately predict CAR-modified cell efficacy (and toxicity) that can correlate with clinical outcomes. Here we review current efforts to develop a Synapse Predicts Efficacy (SPE) system for easy, rapid and cost-effective evaluation of CAR-modified immune cell immunotherapy. Ultimately, we hypothesize the conceptual basis and clinical application of SPE will serve as an important parameter in evaluating CAR immunotherapy and significantly advance precision cancer immunotherapy. Keywords: chimeric antigen receptor, immunotherapy, immunological synapse, and cancer
Immunotherapy and Chimeric Antigen Receptors (CAR) Immunotherapy, mainly defined as harnessing a patient’s own or third party’s immune cells to target tumors, has become a mainstream and powerful treatment option in cancer biology and immunotherapy [1–3]. One prominent advance, engineered Chimeric Antigen Receptor T (CAR-T) cells, was conceptually pioneered in the late * Correspondence: [email protected] 1 Department of Pathology, Immunology and Laboratory Medicine, Rutgers University- New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103, USA 2 Center for Immunity and Inflammation, New Jersey Medical School, Rutgers-The State University of New Jersey, Newark, NJ 07101, USA Full list of author information is available at the end of the article
1980s by Zelig Eshhar [4], and has emerged as a frontline therapeutic modality in immuno-oncology and immunotherapy [5]. Most emblematically, CD19-CAR-T and CD19-CAR-NK, CARs with optimal co-stimulatory signaling and clinical efficacy, have provided an impetus for additional research in both cancer and infectious diseases [6, 7], showing demons
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