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Dual-specific T cells combine proliferation and antitumor activity

Nature Biotechnology volume 20, pages 1221–1227 (2002)Cite this article

Abstract

An effective immune response against cancer requires the activation and expansion of specific T cells. Tumor antigens, however, are generally poor immunogens. To achieve expansion of tumor-reactive T cells in vivo, we used a strategy of generating dual-specific T cells that could respond to a powerful immunogen while also possessing tumor reactivity. We generated dual-specific T cells by genetic modification of alloreactive T cells with a chimeric receptor recognizing folate-binding protein, an ovarian cancer–associated antigen. Mouse dual-specific T cells responded in vitro to both allogeneic antigen and tumor cells expressing folate-binding protein, and expanded in number in vivo in response to immunization with allogeneic cells. Most importantly, the combination of dual-specific T cells and immunization had an antitumor effect in vivo. We also generated human dual-specific T cells and characterized the dual-specific nature of individual clones. Assigning the tasks of expansion and tumor reactivity to different receptors within the same lymphocyte may help to overcome the problem of poor immunogenicity of tumor antigens.

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Figure 1: Reactivity of anti-allogeneic mouse T cells.
Figure 2: In vivo expansion of adoptively transferred alloreactive T cells.
Figure 3: Timing and dose of immunization.
Figure 4: Phenotype, activity, and expansion of dual-specific T cells.
Figure 5: The combination of adoptive transfer of dual-specific T cells and immunization inhibits tumor growth.
Figure 6: Reactivity of human dual-specific T cells.

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Authors and Affiliations

  1. Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD

    Michael H. Kershaw, Jennifer A. Westwood & Patrick Hwu

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  1. Michael H. Kershaw
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  2. Jennifer A. Westwood
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  3. Patrick Hwu
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Correspondence to Patrick Hwu.

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Kershaw, M., Westwood, J. & Hwu, P. Dual-specific T cells combine proliferation and antitumor activity. Nat Biotechnol 20, 1221–1227 (2002). https://doi.org/10.1038/nbt756

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