Bispecific dendritic-T Cell Engager potentiates anti-tumor immunity

Immune checkpoint inhibition treatment using aPD-1 monoclonal antibodies is a promising cancer immunotherapy approach. However, its effect on tumor immunity is narrow, as most patients do not respond to the treatment or suffer from recurrence. We show that the crosstalk between conventional type I dendritic cells (cDC1) and T cells is essential for an effective aPD-1-mediated anti-tumor response. Accordingly, we developed a Bispecific DC-T Cell Engager (BiCE), a reagent that facilitates physical interactions between PD-1+ T-cells and cDC1. BiCE treatment promoted the formation of active dendritic/T cell crosstalk in the tumor and tumor-draining lymph nodes. In vivo, single cell and physical interacting cell analysis demonstrated the distinct and superior immune reprogramming of the tumors and tumor-draining lymph nodes treated with BiCE, as compared to conventional aPD-1 treatment. BiCE introduces a new concept in immunotherapy, bridging of immune cells to potentiate cell circuits and communication pathways needed for effective anti-tumor immunity. Dissecting the effect of BiCE on tumor immune microenvironment using single-cell RNA sequencing. Mice were inoculated with B16 cells and treated with either BiCE,aPD1/Synagis,aPD1 mAb mIg or untreated. Immune cells were harvested from tumors in early and late different time-points and underwent scRNAseq.