Next-Generation Chimeric Antigen Receptor T-Cell Therapy: Going off the Shelf
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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.
This work was supported by grants from the SITC (EMD-Serono Cancer Immunotherapy Clinical Fellowship, PI: M.R.), the AACR (Bristol-Myers Squibb Oncology Fellowship in Clinical Cancer Research, PI: M.R.), the Gabrielle’s Angel Foundation (PI: M.R.), the SIES-AIL (PI: M.R.), the ASH Scholar Award (PI: M.R.), the NCI (K99 CA212302-01A1, PI: M.R. and K12CA166039, PI: S.S.K.), the Predolin Foundation (PI: S.S.K.), the NCCN Young Investigator Award (PI: S.S.K.), and the Mayo Clinic Center for Individualized Medicine (PI: S.S.K.).
M.R. and S.S.K. wrote, reviewed, and accepted the contents of the article.
Compliance with ethical standards
M.R. works under a research collaboration involving the University of Pennsylvania and the Novartis Institute of Biomedical Research, Inc. M.R. and S.S.K. are inventors of intellectual property licensed by the University of Pennsylvania to Novartis.
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