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Med. Sci. 2014, 2(1), 23-36; doi:10.3390/medsci2010023
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Foreign or Domestic CARs: Receptor Ligands as Antigen-Binding Domains

1,†,* , 1
 and
2
1 Cancer Immunology & AIDS Department, Dana-Farber Cancer Institute, Boston, MA 02215, USA 2 Center for Cell and Gene Therapy, Texas Children's Hospital, Houston Methodist Hospital, Baylor College of Medicine, Houston, TX 77030, USA Present address: Jounce Therapeutics, Cambridge, MA 02138, USA.
* Author to whom correspondence should be addressed.
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)
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Abstract

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.
Keywords: chimeric antigen receptor; adoptive immunotherapy; immunology; cancer chimeric antigen receptor; adoptive immunotherapy; immunology; cancer
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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