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Immunotherapy

Treatment of aggressive lymphomas with anti-CD19 CAR T cells

Nature Reviews Clinical Oncology volume 11, pages 685–686 (2014)Cite this article

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Adoptive immunotherapy using T cells genetically engineered to express a chimeric antigen receptor that targets CD19, a B-cell differentiation antigen, has demonstrated impressive efficacy in a range of B-lymphoid malignancies. The latest results demonstrate the potential of this approach in patients with chemotherapy-refractory diffuse large B-cell lymphoma.

Adoptive cell-transfer (ACT) therapy, which involves the ex vivo expansion and reinfusion of tumour-reactive T cells, is emerging as a potential curative treatment for patients with advanced-stage cancer. The ability of ACT to mediate durable complete responses was first demonstrated in patients with melanoma who received surgically-obtained, ex vivo expanded tumour-infiltrating T lymphocytes.1 The capacity to genetically engineer T cells to stably express antigen receptors that convey antitumour reactivity has greatly simplified the generation of therapeutic T cells, enabling translation of this approach to a range of solid and haematological cancers. Clinical trials using genetically-retargeted T cells have used both conventional T-cell receptors (TCRs) and chimeric antigen receptors (CARs); the latter combines into a single chimeric protein the recognition domain of a specific antibody against a tumour-associated antigen and an intracellular signalling domain capable of activating T cells. Because CARs target cells independently of the major histocompatability complex, they offer the possibility for a single genetically-engineered antigen receptor to treat a range of cancer types in a diverse population of patients.

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Figure 1: Treatment of patients with B-cell malignancies using anti-CD19 CAR T cells.

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Affiliations

  1. Center for Cancer Research, Surgery Branch, Immunotherapy Section, 10 Center Drive, Building 10/CRC, Room 3 West-5816, Bethesda, 20892, MA, USA

    Christopher A. Klebanoff, Tori N. Yamamoto & Nicholas P. Restifo

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  1. Christopher A. Klebanoff
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  2. Tori N. Yamamoto
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  3. Nicholas P. Restifo
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Correspondence to Christopher A. Klebanoff.

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The authors declare no competing financial interests.

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Klebanoff, C., Yamamoto, T. & Restifo, N. Treatment of aggressive lymphomas with anti-CD19 CAR T cells. Nat Rev Clin Oncol 11, 685–686 (2014). https://doi.org/10.1038/nrclinonc.2014.190

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