PD-L1 x 4-1BB 双特异性抗体的同时分泌提高分泌 CD19 特异性 T 细胞衔接器的 STAb-T 细胞的抗白血病疗效

Adoptive therapy with CAR-T cells and systemic administration of bispecific T-cell engagers (TCE) have achieved unprecedented success in the treatment of relapsed/refractory (R/R) B-cell malignancies.

However, high relapse rates remain a major challenge. STAb ( S ecretion of T cell-redirecting bispecific Antibodies)-T-cell immunotherapy represents a promising alternative by enabling both polyclonal T-cell recruitment and sustained bispecific antibody release.

Here, we describe an evolution of STAb-T19 therapy, which has demonstrated superior outcomes to those of CAR-T-19 cells in preclinical models of B-ALL, on the basis of the simultaneous secretion of two bispecific antibodies: a CD19 CD3 TCE and a PD-L1 4-1BB bsAb.

The combined approach aims to increase the antitumor efficacy of STAb-T19 cells by blocking the PD-1/PD-L1 axis with conditional 4-1BB costimulation to ensure the long-term persistence of STAb-T cells. Preclinical data show that this combination improves cytotoxic activity and prolongs antileukemic efficacy compared with low-dose single STAb-T therapy.

Our findings suggest that the integration of PD-L1 4-1BB bsAbs into STAb-T19 therapy may maximize efficacy, thereby opening a promising avenue to address resistance and relapse in B-ALL.

Moreover, this approach may pave the way for the development of next-generation cell-based therapies for hematologic and solid malignancies.