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Genome-Editing Technologies in Adoptive T Cell Immunotherapy for Cancer

  • CART and Immunotherapy (M Ruella, Section Editor)
  • Published:
Current Hematologic Malignancy Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

In this review, we discuss the most recent developments in gene-editing technology and discuss their application to adoptive T cell immunotherapy.

Recent Findings

Engineered T cell therapies targeting cancer antigens have demonstrated significant efficacy in specific patient populations. Most impressively, CD19-directed chimeric antigen receptor T cells (CART19) have led to impressive responses in patients with B-cell leukemia and lymphoma. CTL019, or KYMRIAH™ (tisagenlecleucel), a CD19 CAR T cell product developed by Novartis and the University of Pennsylvania, was recently approved for clinical use by the Food and Drug Administration, representing a landmark in the application of adoptive T cell therapies. As CART19 enters routine clinical use, improving the efficacy of this exciting platform is the next step in broader application.

Summary

Novel gene-editing technologies like CRISPR-Cas9 allow facile editing of specific genes within the genome, generating a powerful platform to further optimize the activity of engineered T cells.

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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.), and the NCI (K99 CA212302-01A1, PI: M.R.).

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Authors and Affiliations

  1. Center for Cellular Immunotherapies, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA

    Nathan Singh, Carl H. June & Marco Ruella

  2. Division of Hematology and Oncology, University of Pennsylvania, Philadelphia, PA, USA

    Nathan Singh

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

    Nathan Singh, Carl H. June & Marco Ruella

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

    Junwei Shi, Carl H. June & Marco Ruella

  5. Parker Institute for Cancer Immunotherapy, University of Pennsylvania, Philadelphia, PA, USA

    Carl H. June

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  1. Nathan Singh
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  2. Junwei Shi
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  3. Carl H. June
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Corresponding author

Correspondence to Marco Ruella.

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Conflict of Interest

Nathan Singh and Junwei Shi each declare no potential conflicts of interest.

Carl H. June reports grants from Novartis Pharmaceuticals Corporation and NIH, during the conduct of the study; personal fees from the WIRB/Copernicus Group; grants and others from Tmunity Therapeutics; grants and personal fees from Celldex; and others from Immune Design, all outside the submitted work. In addition, Dr. June has patents 9464140, 9161971, 8975071, 8916381, and 8906682 with royalties paid to Novartis that are related to this work.

Marco Ruella reports grants and other from Novartis, grants from Tmunity, others from NCI, during the conduct of the study. In addition, Dr. Ruella has a patent US20160362472A1 issued, a patent US20150283178A1 issued, a patent US20160068601A1 issued, a patent US20160046724A1 issued, and a patent WO2016164580A1 issued. Dr. Ruella is a section editor for Current Hematologic Malignancy Reports.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the Topical Collection on CART and Immunotherapy

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Singh, N., Shi, J., June, C.H. et al. Genome-Editing Technologies in Adoptive T Cell Immunotherapy for Cancer. Curr Hematol Malig Rep 12, 522–529 (2017). https://doi.org/10.1007/s11899-017-0417-7

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