CAR T cells targeting αvβ3 integrin are effective against advanced cancer in preclinical models.

ABSTRACT: Integrins are heterodimeric receptors that convey cell-to-cell and cell-to-matrix interactions. Integrin αvβ3 is expressed in several tumour entities including melanoma, glioblastoma, breast, pancreatic and prostate cancer, where it promotes tumour cell survival and metastasis. Here, we generated αvβ3-specific chimeric antigen receptor (CAR) T-cells and analysed their antitumour function in pre-clinical models in vitro and in vivo. αvβ3-CARs comprising a super-humanised hLM609 targeting domain with either high or low affinity (hLM609v7, Kd = 3 nM vs. hLM609v11, Kd = 160 nM) and equipped with either a long or a short IgG4-Fc extracellular spacer (229 vs. 12 amino acids) were expressed in CD8+ and CD4+ T-cells through lentiviral transduction. αvβ3-CAR T-cells eliminated αvβ3-positive tumour

SUBMITTER: Wallstabe L 

PROVIDER: S-EPMC6226260 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature