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Double or nothing on cancer immunotherapy

Nature Biotechnology volume 31, pages 33–34 (2013)Cite this article

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Engineered T cells expressing two receptors distinguish malignant cells from healthy cells even in the absence of a tumor-specific antigen.

T cells modified to recognize tumors have the potential to be more effective than antibody drugs as cancer therapeutics1,2 —but only if they can be made to attack tumor cells specifically while sparing normal cells. Unfortunately, in this context immunologists have not been dealt a winning hand as few of the known tumor antigens are truly tumor specific. Most are expressed to some extent on healthy tissues, leading to side effects when they are recognized by engineered T cells. A report in this issue by Kloss et al.3 presents a T-cell immunotherapy strategy designed to avoid such collateral damage. The approach relies on combinatorial recognition of two antigens and careful titration of the strength of signaling through chimeric antigen receptors (CARs). If it can be translated to the clinic, it would enable tumor-specific, T cell–mediated targeting without the need for a tumor-specific antigen.

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Figure 1: Strategy for designing T cells to attack tumor cells and spare normal tissues.

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Authors and Affiliations

  1. Ken-ichi Hanada and Nicholas P. Restifo are in the Center for Cancer Research, National Cancer Institute, US National Institutes of Health, Bethesda, Maryland, USA.,

    Ken-ichi Hanada & Nicholas P Restifo

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  1. Ken-ichi Hanada
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  2. Nicholas P Restifo
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Correspondence to Nicholas P Restifo.

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The authors declare no competing financial interests.

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Hanada, Ki., Restifo, N. Double or nothing on cancer immunotherapy. Nat Biotechnol 31, 33–34 (2013). https://doi.org/10.1038/nbt.2471

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