CiTE antibody for AML.
CiTE antibody for AML.
复制标题
DOI：
10.1182/blood-2018-10-879668
复制
发表时间：
2018-12
期刊：
影响因子：
20.3
通讯作者：
M. Rettig;J. Dipersio
中科院分区：
文献类型：
--
作者：
M. Rettig;J. Dipersio
在本期《血液》杂志中，Herrmann等人通过将程序性细胞死亡蛋白1(PD-1EX)的胞外域与CD3×CD33双特异性T细胞结合蛋白(BIT；见图A-B)融合，开发了一种治疗急性髓系白血病(AML)的新型检查点抑制T细胞结合(CITE)抗体。在体外和小鼠异种移植模型中，PD-1EX结构域的掺入增加了人T细胞的激活，并导致了对CD33+/PD-L1+细胞的有效细胞毒作用。重要的是，PD-1EX结构域不足以将T细胞重定向到缺乏CD33靶点的PD-L1+细胞。CD33+/PD-L1+细胞的这种优先靶向应该会减少与抗PD1/PD-L1单抗(MAbs)的全球检查点封锁的靶上/肿瘤外效应相关的免疫相关不良事件。
In this issue of Blood , Herrmann et al 1 have developed a novel checkpoint inhibitory T-cell–engaging (CiTE) antibody for acute myeloid leukemia (AML) by fusing the extracellular domain of programmed cell death protein 1 (PD-1 ex ) to a CD3 × CD33 bispecific T-cell engager (BiTE; see figure panels A-B). Incorporation of the PD-1 ex domain increased human T-cell activation and led to efficient cytotoxicity against CD33 + /PD-L1 + cells in vitro and in a murine xenograft model. Importantly, the PD-1 ex domain is not sufficient to redirect T cells to PD-L1 + cells lacking the CD33 target. This preferential targeting of CD33 + /PD-L1 + cells should reduce the immune-related adverse events associated with on-target/off-tumor effects of global checkpoint blockade with anti-PD1/PD-L1 monoclonal antibodies (mAbs).