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Immunotherapy through TCR gene transfer

Abstract

The antigen specificity of T lymphocytes is dictated solely by the T cell receptor (TCR) α and β chains. Consequently, genetic transfer of TCR chains may be an appealing strategy with which to impose a desirable virus- or tumor-antigen specificity onto cytotoxic or helper T cell populations. We describe here the genetic introduction of a virus-specific TCR into peripheral T cells in a mouse model system. These experiments showed that T cells redirected by TCR gene transfer expanded upon viral infection of mice and efficiently homed to effector sites. In this setting, TCR gene transfer was not associated with any significant autoimmune pathology. In addition, small numbers of TCR-transduced T cells promoted the rejection of antigen-expressing tumors in vivo. These data suggest that the redirection of T cells by TCR gene transfer is a viable strategy for the rapid induction of virus- or tumor-specific immunity.

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Figure 1: Genetic transfer of TCR chains resulted in expression of functional TCRs.
Figure 2: In vivo expansion of TCR-transduced CD8+ T cells upon specific influenza A infection.
Figure 3: Distribution of expanded TCR-transduced cells.
Figure 4: In vivo anti-tumor activity of TCR-transduced cells.

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Acknowledgements

We thank M. Toebes for preparation of the MHC tetramers; C. de Goeij, C. Boersema, J. Bulthuis and M. Tjin-A-Koeng for histotechnical assistance; G. Rimmelzwaan for growing and titrating the various influenza strains; T. Kitamura for the pMX retroviral vector; G. Nolan for the Phoenix-E cell line; and E. Noteboom and A. Pfauth for assistance with flow cytometry analysis. Supported by the Dutch Cancer Society (NKI 97-1442 and NKI 99-2036) and the Netherlands Organization for Scientific Research (NWO pioneer grant 00-03).

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Correspondence to Ton N. M. Schumacher.

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Kessels, H., Wolkers, M., van den Boom, M. et al. Immunotherapy through TCR gene transfer. Nat Immunol 2, 957–961 (2001). https://doi.org/10.1038/ni1001-957

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