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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
Present address: Jounce Therapeutics, Cambridge, MA 02138, USA.
* Author to whom correspondence should be addressed.
Received: 3 December 2013; in revised form: 22 January 2014 / Accepted: 22 January 2014 / Published: 28 January 2014
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
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MDPI and ACS Style
Shaffer, D.R.; Zhou, P.; Gottschalk, S. Foreign or Domestic CARs: Receptor Ligands as Antigen-Binding Domains. Med. Sci. 2014, 2, 23-36.
Shaffer DR, Zhou P, Gottschalk S. Foreign or Domestic CARs: Receptor Ligands as Antigen-Binding Domains. Medical Sciences. 2014; 2(1):23-36.
Shaffer, Donald R.; Zhou, Penghui; Gottschalk, Stephen. 2014. "Foreign or Domestic CARs: Receptor Ligands as Antigen-Binding Domains." Med. Sci. 2, no. 1: 23-36.