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Genetically Modified T-Cell Therapy for Osteosarcoma

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Current Advances in Osteosarcoma

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 804))

Abstract

T-cell immunotherapy may offer an approach to improve outcomes for patients with osteosarcoma, who fail current therapies. In addition, it has the potential to reduce treatment-related complications for all patients. Generating tumor-specific T cells with conventional antigen presenting cells ex vivo is time consuming and often results in T-cell products with a low frequency of tumor-specific T cells. In addition, the generated T cells remain sensitive to the immunosuppressive tumor microenvironment. Genetic modification of T cells is one strategy to overcome these limitations. For example, T cells can be genetically modified to render them antigen specific, resistant to inhibitory factors, or increase their ability to home to tumor sites. Most genetic modification strategies have only been evaluated in preclinical models, however early phase clinical trials are in progress. In this chapter we review the current status of gene-modified T-cell therapy with special focus on osteosarcoma, highlighting potential antigenic targets, preclinical and clinical studies, and strategies to improve current T-cell therapy approaches.

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Acknowledgement

The authors are supported by NIH grants 1R01CA148748-01A1, 1R01CA173750-01, P01CA094237, CPRIT RP101335, Alex’s Lemonade Stand Foundation, The V Foundation, and Cookies for Kid’s Cancer.

Conflict of interest. The Center for Cell and Gene Therapy has a research collaboration with Celgene and bluebird bio. CD and SG have patent applications in the field of T-cell and gene-modified T-cell therapy for cancer.

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Authors and Affiliations

  1. Center for Cell and Gene Therapy, Houston Methodist, Texas Children’s Hospital, Baylor College of Medicine, 1102 Bates Street, Suite 1770, Houston, TX, 77030, USA

    Christopher DeRenzo & Stephen Gottschalk

  2. Texas Children’s Cancer Center, Texas Children’s Hospital, Baylor College of Medicine, Houston, TX, 77030, USA

    Christopher DeRenzo & Stephen Gottschalk

  3. Department of Pediatrics, Baylor College of Medicine, Houston, TX, 77030, USA

    Christopher DeRenzo & Stephen Gottschalk

  4. Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, 77030, USA

    Stephen Gottschalk

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  1. Christopher DeRenzo
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  2. Stephen Gottschalk
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Correspondence to Stephen Gottschalk .

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Editors and Affiliations

  1. Division of Pediatrics, Department of Cancer Biology, The Mary V. and John A. Reilly Distinguished Chair, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA

    Eugenie S. Kleinerman, M.D.

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DeRenzo, C., Gottschalk, S. (2014). Genetically Modified T-Cell Therapy for Osteosarcoma. In: Kleinerman, M.D., E. (eds) Current Advances in Osteosarcoma. Advances in Experimental Medicine and Biology, vol 804. Springer, Cham. https://doi.org/10.1007/978-3-319-04843-7_18

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