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Review
. 2018 Jun;31(2):176-183.
doi: 10.1016/j.beha.2018.03.003. Epub 2018 Mar 27.

Advances in the use of natural receptor- or ligand-based chimeric antigen receptors (CARs) in haematologic malignancies

Joana M Murad  1 , David J Graber  2 , Charles L Sentman  3
Affiliations
Review

Advances in the use of natural receptor- or ligand-based chimeric antigen receptors (CARs) in haematologic malignancies

Joana M Murad et al. Best Pract Res Clin Haematol. 2018 Jun.

Abstract

Chimeric antigen receptors (CAR)-T cell therapy has recently made promising advances towards treatment of B-cell malignancies. This approach makes use of an antibody-derived single chain variable fragment (scFv)-based CAR to target the CD19 antigen. Currently scFvs are the most common strategy for creation of CARs, but tumor cells can also be targeted using non-antibody based approaches with designs focused on the interaction between natural receptors and their ligands. This emerging strategy has been used in unique ways to target multiple tumor types, including solid and haematological malignancies. In this review, we will highlight the performance of receptor-ligand combinations as designs for CARs to treat cancer, with a particular focus on haematologic malignancies.

Keywords: Cell therapy; Cytokines; Immunotherapy; NKG2D; T cell.

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Conflict of interest statement

Conflict of interest

C.L.S. has patents and financial interests in NK receptor-based CAR therapies. C.L.S. is a scientific founder for Celdara Medical, a consultant, and receives research support from Celdara Medical. J.M.M. is employed by Celdara Medical, which has a material financial interest in NK receptor-based CAR intellectual property assigned to the Trustees of Dartmouth College.

Figures

Figure 1.
Figure 1.
Schematic structure of receptor- and ligand-based chimeric antigen receptors. Receptor-based CARs: (A) native protein extracellular domain bound to either CD8 or CD28 transmembrane, followed by intracellular signaling domain; and (B) complete native receptor, including both extracellular and transmembrane domains, followed by intracellular signaling domain. (C) Ligand-based CAR: ligand molecule is bound to either CD8 or CD28 transmembrane, followed by intracellular signaling domain.
See this image and copyright information in PMC

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