title: The integrin αvβ6: a novel target for CAR T-cell immunotherapy?
abstract: Immunotherapy of cancer using chimeric antigen receptor (CAR) T-cells is a rapidly expanding field. CARs are fusion molecules that couple the binding of a tumour-associated cell surface target to the delivery of a tailored T-cell activating signal. Re-infusion of such genetically engineered T-cells to patients with haematological disease has demonstrated unprecedented response rates in Phase I clinical trials. However, such successes have not yet been observed using CAR T-cells against solid malignancies and this is, in part, due to a lack of safe tumour-specific targets. The αvβ6 integrin is strongly up-regulated in multiple solid tumours including those derived from colon, lung, breast, cervix, ovaries/fallopian tube, pancreas and head and neck. It is associated with poorer prognosis in several cancers and exerts pro-tumorigenic activities including promotion of tumour growth, migration and invasion. By contrast, physiologic expression of αvβ6 is largely restricted to wound healing. These attributes render this epithelial-specific integrin a highly attractive candidate for targeting using immunotherapeutic strategies such as CAR T-cell adoptive immunotherapy. This mini-review will discuss the role and expression of αvβ6 in cancer, as well as its potential as a therapeutic target.
authors.affiliation: King's College London, King's Health Partners Integrated Cancer Centre, Department of Research Oncology, Guy's Hospital, Great Maze Pond, London SE1 9RT, U.K. lynsey.whilding@kcl.ac.uk.
authors.forename: Lynsey M
authors.initials: LM
authors.lastname: Whilding
authors.affiliation: Centre for Tumour Biology, John Vane Science Centre, Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, U.K.
authors.forename: Sabari
authors.initials: S
authors.lastname: Vallath
authors.affiliation: King's College London, King's Health Partners Integrated Cancer Centre, Department of Research Oncology, Guy's Hospital, Great Maze Pond, London SE1 9RT, U.K. Department of Immunology, Barnet Hospital, Royal Free London NHS Foundation Trust, Barnet EN5 3DJ, U.K. Department of Clinical Immunology and Allergy, King's College Hospital NHS Foundation Trust, Denmark Hill, London SE5 9RS, U.K.
authors.forename: John
authors.initials: J
authors.lastname: Maher
mesh_terms: D000951:Antigens, Neoplasm / Q000737:chemistry / Q000276:immunology* / Q000502:physiology; D014408:Biomarkers, Tumor / Q000276:immunology; D006801:Humans; D007167:Immunotherapy / Q000009:adverse effects; D016023:Integrins / Q000737:chemistry / Q000276:immunology* / Q000502:physiology; D009369:Neoplasms / Q000276:immunology / Q000628:therapy; D011379:Prognosis; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D016023:Integrins; D011948:Receptors, Antigen, T-Cell; C073878:integrin alphavbeta6
keywords: T-cells; cancer; chimeric antigen receptor; immunotherapy; integrins; αvβ6