以 HLA-C*07:01 限制性 T 细胞受体靶向黑色素瘤相关抗原 CSPG4

The TCRs of two CSPG4-reactive T-cell clones (11C/73 and 2C/165) restricted by the highly prevalent HLA-C*07:01 allele were isolated and the respective αβTCR pairs were retrovirally expressed in CRISPR/Cas9-edited TCR-knockout T cells for functional testing. We also combined alpha and beta TCR chains derived from 11C/73 and 2C/165 in a cross-over fashion to assess for hemichain dominance. CSPG4 + melanoma, glioblastoma and lung cancer cell lines were identified and, if negative, retrovirally transduced with HLA-C*07:01.

Functional tests confirmed specific recognition of CSPG4 + HLA-C*07:01 + target cells by the αβTCR retrieved from the parental T-cell clones and in part also by the cross-over TCR construct 2Cα-11Cβ. Despite high surface expression, the 11Cα-2Cβ combination, however, was not functional. DISCUSSION: Collectively, 11C/73- and 2C/165-expressing T cells specifically and efficiently recognized CSPG4 + HLA-C*07:01 + cancer cells which warrants further preclinical and clinical evaluation of these TCRs.