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

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Abstract

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.

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Acknowledgements

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.).

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Authors and Affiliations

  1. Center for Cellular Immunotherapies, Perelman School of Medicine at the University of Pennsylvania, Smilow Center for Translational Research, 8-112, 3400 Civic Center Boulevard, Philadelphia, PA, 19104, USA

    Marco Ruella

  2. Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA

    Marco Ruella

  3. Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA

    Marco Ruella

  4. Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN, USA

    Saad S. Kenderian

  5. Department of Immunology, Mayo Clinic, Rochester, MN, USA

    Saad S. Kenderian

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M.R. and S.S.K. wrote, reviewed, and accepted the contents of the article.

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Correspondence to Marco Ruella.

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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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Ruella, M., Kenderian, S.S. Next-Generation Chimeric Antigen Receptor T-Cell Therapy: Going off the Shelf. BioDrugs 31, 473–481 (2017). https://doi.org/10.1007/s40259-017-0247-0

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