以色列魏茨曼科学研究所Rony Dahan和Ido Amit共同合作，近期取得重要工作进展。他们研究提出，双特异性树突状T细胞接合剂可增强抗肿瘤免疫。相关研究成果2024年1月18日在线发表于《细胞》杂志上。

据介绍，使用aPD-1单克隆抗体的免疫检查点抑制治疗是一种很有前途的癌症免疫疗法。然而，它对肿瘤免疫的影响很小，因为大多数患者对治疗没有反应或复发。

研究人员发现，传统的I型树突状细胞（cDC1）和T细胞之间的相互作用对于有效的aPD-1介导的抗肿瘤反应至关重要。因此，研究团队开发了一种双特异性DC-T细胞接合器（BiCE），这是一种促进PD-1⁺ T细胞和cDC1之间物理相互作用的试剂。BiCE治疗促进肿瘤和肿瘤引流淋巴结中活性树突/T细胞相互作用的形成。在体内，单细胞和物理相互作用的细胞分析表明，与传统的aPD-1治疗相比，BiCE治疗的肿瘤和肿瘤引流淋巴结具有独特且优越的免疫重编程。

总之，通过桥接免疫细胞，BiCE增强了有效抗肿瘤免疫所需的细胞回路和通讯途径。

附：英文原文

Title: Bispecific dendritic-T cell engager potentiates anti-tumor immunity

Author: Yuval Shapir Itai, Oren Barboy, Ran Salomon, Akhiad Bercovich, Ken Xie, Eitan Winter, Tamar Shami, Ziv Porat, Neta Erez, Amos Tanay, Ido Amit, Rony Dahan

Issue&Volume: 2024/01/18

Abstract: Immune checkpoint inhibition treatment using aPD-1 monoclonal antibodies is a promisingcancer immunotherapy approach. However, its effect on tumor immunity is narrow, asmost patients do not respond to the treatment or suffer from recurrence. We show thatthe crosstalk between conventional type I dendritic cells (cDC1) and T cells is essentialfor an effective aPD-1-mediated anti-tumor response. Accordingly, we developed a bispecificDC-T cell engager (BiCE), a reagent that facilitates physical interactions betweenPD-1+ T cells and cDC1. BiCE treatment promotes the formation of active dendritic/T cellcrosstalk in the tumor and tumor-draining lymph nodes. In vivo, single-cell and physical interacting cell analysis demonstrates the distinct andsuperior immune reprogramming of the tumors and tumor-draining lymph nodes treatedwith BiCE as compared to conventional aPD-1 treatment. By bridging immune cells, BiCEpotentiates cell circuits and communication pathways needed for effective anti-tumorimmunity.

DOI: 10.1016/j.cell.2023.12.011

Source: https://www.cell.com/cell/fulltext/S0092-8674(23)01343-0