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Glycan-directed CAR-T cells

Steentoft, Catharina
King, Tiffany R
Mandel, Ulla
June, Carl H
Posey, Avery D (Jr)
Published in Glycobiology. 2018, vol. 28, no. 9, p. 656-669
Abstract Cancer immunotherapy is rapidly advancing in the treatment of a variety of hematopoietic cancers, including pediatric acute lymphoblastic leukemia and diffuse large B cell lymphoma, with chimeric antigen receptor (CAR)-T cells. CARs are genetically encoded artificial T cell receptors that combine the antigen specificity of an antibody with the machinery of T cell activation. However, implementation of CAR technology in the treatment of solid tumors has been progressing much slower. Solid tumors are characterized by a number of challenges that need to be overcome, including cellular heterogeneity, immunosuppressive tumor microenvironment (TME), and, in particular, few known cancer-specific targets. Post-translational modifications that differentially occur in malignant cells generate valid cell surface, cancer-specific targets for CAR-T cells. We previously demonstrated that CAR-T cells targeting an aberrant O-glycosylation of MUC1, a common cancer marker associated with changes in cell adhesion, tumor growth and poor prognosis, could control malignant growth in mouse models. Here, we discuss the field of glycan-directed CAR-T cells and review the different classes of antibodies specific for glycan-targeting, including the generation of high affinity O-glycopeptide antibodies. Finally, we discuss historic and recently investigated glycan targets for CAR-T cells and provide our perspective on how targeting the tumor glycoproteome and/or glycome will improve CAR-T immunotherapy.
Keywords AnimalsHumansImmunotherapyNeoplasms/immunology/therapyPolysaccharides/immunologyReceptors, Antigen, T-Cell/immunology
PMID: 29370379
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STEENTOFT, Catharina et al. Glycan-directed CAR-T cells. In: Glycobiology, 2018, vol. 28, n° 9, p. 656-669. doi: 10.1093/glycob/cwy008

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Deposited on : 2021-03-22

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