The integrin αvβ6: a novel target for CAR T-cell immunotherapy?. (11th April 2016)

• Record Type: Journal Article
• Authors: Whilding, Lynsey M.; Vallath, Sabari; Maher, John
• Is Part Of: Biochemical Society transactions. Volume 44:Number 2(2016)
• Page Start: 349
• Page End: 355
• Publication Date: 2016-04-11
• Subjects: αvβ6 -- cancer -- chimeric antigen receptor -- immunotherapy -- integrins -- T-cells; Biochemistry -- Congresses; 572
• DOI: 10.1042/BST20150249
• Languages: English
• ISSNs: 0300-5127

Abstract

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.