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Med. Sci. 2014, 2(1), 23-36;

Foreign or Domestic CARs: Receptor Ligands as Antigen-Binding Domains

Cancer Immunology & AIDS Department, Dana-Farber Cancer Institute, Boston, MA 02215, USA
Center for Cell and Gene Therapy, Texas Children's Hospital, Houston Methodist Hospital, Baylor College of Medicine, Houston, TX 77030, USA
Author to whom correspondence should be addressed.
Present address: Jounce Therapeutics, Cambridge, MA 02138, USA.
Received: 3 December 2013 / Revised: 22 January 2014 / Accepted: 22 January 2014 / Published: 28 January 2014
(This article belongs to the Special Issue Recent Advances in Cellular Immunotherapy)
PDF [358 KB, uploaded 28 January 2014]


Chimeric antigen receptors (CARs) are increasingly being used in clinical trials to treat a variety of malignant conditions and recent results with CD19-specific CARs showing complete tumor regressions has sparked the interest of researchers and the public alike. Traditional CARs have been generated using single-chain variable fragments (scFv), often derived from murine monoclonal antibodies, for antigen specificity. As the clinical experience with CAR T cells grows, so does the potential for unwanted immune responses against the foreign transgene. Strategies that may reduce the immunogenicity of CAR T cells are humanization of the scFv and the use of naturally occurring receptor ligands as antigen-binding domains. Herein, we review the experience with alternatively designed CARs that contain receptor ligands rather than scFv. While most of the experiences have been in the pre-clinical setting, clinical data is also emerging. View Full-Text
Keywords: chimeric antigen receptor; adoptive immunotherapy; immunology; cancer chimeric antigen receptor; adoptive immunotherapy; immunology; cancer

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This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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Shaffer, D.R.; Zhou, P.; Gottschalk, S. Foreign or Domestic CARs: Receptor Ligands as Antigen-Binding Domains. Med. Sci. 2014, 2, 23-36.

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