Ramos Rodrigo Nalio, Couto Samuel Campanelli Freitas, Oliveira Theo Gremen M, Klinger Paulo, Braga Tarcio Teodoro, Rego Eduardo Magalhães, Barbuto José Alexandre M, Rocha Vanderson
Laboratory of Medical Investigation in Pathogenesis and Directed Therapy in Onco-Immuno-Hematology (LIM-31), Departament of Hematology and Cell Therapy, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, University of São Paulo, São Paulo, Brazil.
Instituto D'Or de Ensino e Pesquisa, São Paulo, Brazil.
Front Cell Dev Biol. 2021 Dec 10;9:784421. doi: 10.3389/fcell.2021.784421. eCollection 2021.
Chimeric antigen receptor (CAR) engineering for T cells and natural killer cells (NK) are now under clinical evaluation for the treatment of hematologic cancers. Although encouraging clinical results have been reported for hematologic diseases, pre-clinical studies in solid tumors have failed to prove the same effectiveness. Thus, there is a growing interest of the scientific community to find other immune cell candidate to express CAR for the treatment of solid tumors and other diseases. Mononuclear phagocytes may be the most adapted group of cells with potential to overcome the dense barrier imposed by solid tumors. In addition, intrinsic features of these cells, such as migration, phagocytic capability, release of soluble factors and adaptive immunity activation, could be further explored along with gene therapy approaches. Here, we discuss the elements that constitute the tumor microenvironment, the features and advantages of these cell subtypes and the latest studies using CAR-myeloid immune cells in solid tumor models.
用于T细胞和自然杀伤细胞(NK)的嵌合抗原受体(CAR)工程目前正在进行治疗血液系统癌症的临床评估。尽管已有关于血液系统疾病的令人鼓舞的临床结果报道,但实体瘤的临床前研究未能证明同样有效。因此,科学界越来越有兴趣寻找其他免疫细胞候选者来表达CAR,以治疗实体瘤和其他疾病。单核吞噬细胞可能是最适合的细胞群体,有潜力克服实体瘤所造成的致密屏障。此外,这些细胞的内在特性,如迁移、吞噬能力、可溶性因子的释放和适应性免疫激活,可与基因治疗方法一起进一步探索。在此,我们讨论构成肿瘤微环境的要素、这些细胞亚型的特征和优势,以及在实体瘤模型中使用CAR髓系免疫细胞的最新研究。