Chimeric antigen receptor therapy for cancer - PubMed (original) (raw)

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Chimeric antigen receptor therapy for cancer

David M Barrett et al. Annu Rev Med. 2014.

Abstract

Improved outcomes for patients with cancer hinge on the development of new targeted therapies with acceptable short-term and long-term toxicity. Progress in basic, preclinical, and clinical arenas spanning cellular immunology, synthetic biology, and cell-processing technologies has paved the way for clinical applications of chimeric antigen receptor-based therapies. This new form of targeted immunotherapy merges the exquisite targeting specificity of monoclonal antibodies with the potent cytotoxicity and long-term persistence provided by cytotoxic T cells. Although this field is still in its infancy, clinical trials have already shown clinically significant antitumor activity in neuroblastoma, chronic lymphocytic leukemia, and B cell lymphoma, and trials targeting a variety of other adult and pediatric malignancies are under way. Ongoing work is focused on identifying optimal tumor targets and on elucidating and manipulating both cell- and host-associated factors to support expansion and persistence of the genetically engineered cells in vivo. The potential to target essentially any tumor-associated cell-surface antigen for which a monoclonal antibody can be made opens up an entirely new arena for targeted therapy of cancer.

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Conflict of interest statement

DISCLOSURE STATEMENT

The University of Pennsylvania has entered into a partnership with Novartis for the development of chimeric antigen receptors. This partnership is managed in accordance with the University of Pennsylvania’s Conflict of Interest Policy. All authors are in compliance with this policy.

Figures

Figure 1

Figure 1

Antibodies can bind to surface antigens expressed on tumor cells. Chimeric antigen receptors (CARs) have a single-chain antibody fragment (scFv), expressed in tandem with signaling elements derived from the T cell receptor (TCR) and costimulatory domains such as 4-1BB and CD28.

Figure 2

Figure 2

Chimeric antigen receptor (CAR) therapy is similar to an autologous bone marrow transplantation procedure. T cells are collected from the patient by apheresis, and the T cells are expanded and genetically modified using several approaches before they are returned to the patient. Abbreviation: APCs, antigen-presenting cells.

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