Next-Generation Chimeric Antigen Receptor T-Cell Therapy: Going off the Shelf

• Published in: BioDrugs : clinical immunotherapeutics, biopharmaceuticals, and gene therapy Vol. 31; no. 6; pp. 473 - 481
• Main Authors: Ruella, Marco, Kenderian, Saad S.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.12.2017; Springer Nature B.V
• Subjects: Acute lymphoblastic leukemia; Antibodies; Antigens; Antigens, CD19; Autografts; Biomedical and Life Sciences; Biomedicine; Cancer; Cancer Research; Cancer therapies; CD19 antigen; Cell- and Tissue-Based Therapy - methods; Chimeric antigen receptors; Current Opinion; FDA approval; Gene Editing - methods; Genomes; Graft rejection; Graft vs Host Disease - prevention & control; Graft-versus-host reaction; Humans; Immune system; Immunotherapy; Leukemia; Lymphatic leukemia; Lymphocytes; Lymphocytes T; Lymphoma; Manufacturing; Molecular Medicine; Patients; Pediatrics; Pharmacotherapy; Precursor Cell Lymphoblastic Leukemia-Lymphoma - therapy; Receptors, Antigen, T-Cell - genetics; Receptors, Antigen, T-Cell - immunology; T cell receptors; T-Lymphocytes - transplantation; Transplantation, Homologous; Viral infections
• ISSN: 1173-8804; 1179-190X
• DOI: 10.1007/s40259-017-0247-0

Autologous, patient-specific chimeric antigen receptor T-cell (CART) therapy has emerged as a powerful and potentially curative therapy for cancer, especially for CD19-positive hematological malignancies. Indeed, on August 30, 2017, the University of Pennsylvania-designed CD19-directed CART (CART-19) cell therapy (CTL019, tisagenlecleucel-t, Kymriah - Novartis) became the first CART therapy approved by the Food and Drug Administration (FDA) for acute lymphoblastic leukemia. However, the development of CART technology and its wider application is partly limited by the patient-specific nature of such a platform and by the time required for manufacturing. The efficacious generation of universal allogeneic CART cells would overcome these limitations and represent a major advance in the field. However, several obstacles in the generation of universal CART cells need to be overcome, namely the risk of CART rejection and the risk of graft-versus-host disease mediated by the allogeneic CART. In this review, we discuss the different strategies being employed to generate universal CART and provide our perspective on the successful development of a truly off-the-shelf CART product.