嵌合抗原受体T（CAR-T）细胞疗法在血液肿瘤的治疗中取得了显着的成功。然而，鉴于实体瘤的独特特征，特别是异质性、代谢侵袭性和肿瘤微环境（TME）中较少的免疫细胞，CAR-T细胞在实体瘤中的实际应用仍然是一个具有挑战性的问题。与此同时，尽管抗PD-1单克隆抗体（mAb）已显示出临床疗效，但大多数mAb对实体瘤的临床益处也有限，这主要是由于TME中缺乏免疫细胞的问题。因此，将靶向免疫活性细胞浸润到 TME 中可以对 mAb 产生协同功效。我们提出了一种实体瘤治疗的组合策略，该策略结合装甲 T 细胞在表面表达 Fc-gamma 受体 I (FcγRI) 片段以进行靶向治疗具有治疗作用的单克隆抗体可用于多种肿瘤。以CD20和HER-2为靶点，采用流式细胞术、ELISA等方法表征联合药物的体外和体内药效及潜在机制。装甲T细胞与Rituximab相应抗体的结合和预处理帕妥珠单抗发挥了深远的抗肿瘤作用，这被证明是通过协同产生的抗体依赖性细胞毒性（ADCC）作用介导的。同时，mAb 能够通过预处理携带装甲 T 细胞，用于细胞衍生异种移植 (CDX) 模型中的 TME 浸润。这种组合策略显示，由于抗体剂量的减少，安全性显着提高。更重要的是，本策略可以通过简单配对工程化 T 细胞和传统抗体，成为广泛癌症治疗的多功能工具。版权所有 © 2024 Tang, Sun, Li, Yu,Meng,Zhang,Ma,Zeng 、李、刘、徐、郭。

Chimeric antigen receptor T (CAR-T) cell therapies have achieved remarkable success in the treatment of hematological tumors. However, given the distinct features of solid tumors, particularly heterogeneity, metabolic aggressiveness, and fewer immune cells in tumor microenvironment (TME), the practical utility of CAR-T cells for solid tumors remains as a challenging issue. Meanwhile, although anti-PD-1 monoclonal antibody (mAb) has shown clinical efficacy, most mAbs also show limited clinical benefits for solid tumors due mainly to the issues associated with the lack of immune cells in TME. Thus, the infiltration of targeted immunological active cells into TME could generate synergistic efficacy for mAbs.We present a combinational strategy for solid tumor treatment, which combines armored-T cells to express Fc-gamma receptor I (FcγRI) fragment on the surfaces for targeting various tumors with therapeutically useful mAbs. Choosing CD20 and HER-2 as the targets, we characterized the in vitro and in vivo efficacy and latent mechanism of the combination drug by using flow cytometry, ELISA and other methods.The combination and preprocessing of armored T-cells with corresponding antibody of Rituximab and Pertuzumab exerted profound anti-tumor effects, which is demonstrated to be mediated by synergistically produced antibody-dependent cellular cytotoxicity (ADCC) effects. Meanwhile, mAb was able to carry armored-T cell by preprocessing for the infiltration to TME in cell derived xenograft (CDX) model.This combination strategy showed a significant increase of safety profiles from the reduction of antibody doses. More importantly, the present strategy could be a versatile tool for a broad spectrum of cancer treatment, with a simple pairing of engineered T cells and a conventional antibody.Copyright © 2024 Tang, Sun, Li, Yu, Meng, Zhang, Ma, Zeng, Li, Liu, Xu and Guo.