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Targeted cellular immunotherapy for T cell malignancies

Nature Medicine volume 23, pages 1402–1403 (2017)Cite this article

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In a recent study, Maciocia et al. develop a novel T cell receptor beta (TCRB) constant C1-chain-directed cellular immunotherapy for the treatment of T cell malignancies.

Immunotherapy, a therapeutic modality that directs the immune system against tumor cells for the treatment of cancer, has been a front-line treatment for B cell lymphoma for almost two decades. Antibodies against CD20, a pan–B cell surface antigen, trigger effective antitumor responses in mature B cell tumors, and bispecific antibodies that bridge T cells and B cells can effectively direct cellular immune responses against malignant B cells1. In addition, cellular immunotherapy with T cells expressing chimeric antigen receptors (CAR)—engineered single-chain proteins capable of eliciting immune activation and designed to engage with a specific antigen of choice—has shown efficacy against an expanding number of B cell non-Hodgkin lymphomas1. However, pan–B cell–directed CAR T cells ablate both normal and tumor B cells, resulting in B cell immunosuppression. Although this can be managed clinically, a more targeted strategy with significant promise is the use of CAR T cells with specificity against the immunoglobulin κ light chain. Using this approach, both normal and malignant cells expressing κ light immunoglobulins are ablated by κ-light-chain-directed CAR T cells, yet normal λ-light-chain-expressing lymphocytes are spared, precluding the development of overt B cell immunodeficiency2.

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Figure 1: Principles of anti-TCRB-C1 CAR T cell therapy.

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Authors and Affiliations

  1. Institute for Cancer Genetics, Columbia University, New York, New York, USA

    Teresa Palomero & Adolfo Ferrando

  2. Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York, USA

    Teresa Palomero & Adolfo Ferrando

  3. Department of Pediatrics, Columbia University Medical Center, New York, New York, USA

    Adolfo Ferrando

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  1. Teresa Palomero
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  2. Adolfo Ferrando
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Correspondence to Adolfo Ferrando.

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The authors declare no competing financial interests.

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Palomero, T., Ferrando, A. Targeted cellular immunotherapy for T cell malignancies. Nat Med 23, 1402–1403 (2017). https://doi.org/10.1038/nm.4458

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