胶质母细胞瘤 EGFRvIII 靶向 CAR-T 细胞输注产品中 PD1 表达与临床应答相关

The epidermal growth factor receptor variant III (EGFRvIII) has been investigated as a therapeutic target for chimeric antigen receptor (CAR) T cell therapy in glioblastoma. Earlier research demonstrated that phenotypic and genotypic characteristics in T cells and CAR T product predicted therapeutic success in hematologic malignancies, to date no determinants for clinical response in solid tumors have been identified.

We analyzed apheresis and infusion products from the first-in-human trial of EGFRvIII-directed CAR T for recurrent glioblastoma (NCT02209376) by flow cytometry. Clinical response was quantified via engraftment in peripheral circulation and progression-free survival (PFS), as determined by the time from CAR T infusion to first radiographic evidence of progression. The CD4 + CAR T cell population in patient infusion products demonstrated PD1 expression which positively correlated with AUC engraftment and PFS.

On immune checkpoint inhibitor analysis, CTLA-4, TIM3, and LAG3 did not exhibit significant associations with engraftment or PFS. The frequencies of PD1 + GZMB + and PD1 + HLA-DR + CAR T cells in the CD4 + infusion products were directly proportional to AUC and PFS. No significant associations were observed within the apheresis products. In summary, PD1 in CAR T infusion products predicted peripheral engraftment and PFS in recurrent glioblastoma.