TY - JOUR
T1 - Bispecific dendritic-T cell engager potentiates anti-tumor immunity
AU - Shapir Itai, Yuval
AU - Barboy, Oren
AU - Salomon, Ran
AU - Bercovich, Akhiad
AU - Xie, Ken
AU - Winter, Eitan
AU - Shami, Tamar
AU - Porat, Ziv
AU - Erez, Neta
AU - Tanay, Amos
AU - Amit, Ido
AU - Dahan, Rony
N1 - Publisher Copyright:
© 2023 Elsevier Inc.
PY - 2024/1/18
Y1 - 2024/1/18
N2 - 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 promotes 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 demonstrates the distinct and superior immune reprogramming of the tumors and tumor-draining lymph nodes treated with BiCE as compared to conventional aPD-1 treatment. By bridging immune cells, BiCE potentiates cell circuits and communication pathways needed for effective anti-tumor immunity.
AB - 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 promotes 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 demonstrates the distinct and superior immune reprogramming of the tumors and tumor-draining lymph nodes treated with BiCE as compared to conventional aPD-1 treatment. By bridging immune cells, BiCE potentiates cell circuits and communication pathways needed for effective anti-tumor immunity.
KW - PD-1
KW - T cell exhaustion
KW - bispecific antibody
KW - cancer immunotherapy
KW - dendritic cells
KW - immune checkpoint inhibition
KW - therapeutic antibody
UR - http://www.scopus.com/inward/record.url?scp=85182569575&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2023.12.011
DO - 10.1016/j.cell.2023.12.011
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C2 - 38242085
AN - SCOPUS:85182569575
SN - 0092-8674
VL - 187
SP - 375-389.e18
JO - Cell
JF - Cell
IS - 2
ER -
