Lum Lawrence G, Davol Pamela A
Immunotherapy Program, Adele R. Deof Cancer Center, Roger Williams Hospital, Providence, RI 02908, USA.
Cancer Chemother Biol Response Modif. 2005;22:273-91. doi: 10.1016/s0921-4410(04)22013-0.
The development of BiAbs for therapeutic applications in cancer shows promise. As our understanding of effector cell receptor biology for triggering of cytotoxic functions improves and the behavior of TAA and the targeting antibody engagement is elucidated, customized BiAb reagents can be engineered to optimize in vivo or ex vivo arming of T cells for targeting tumors. Additionally, other variables that require consideration in the equation for successful T cell immunotherapy include: the type of effector cells, their state of activation, the type of effector receptor being activated or tareeted. the presence of Tregs, the affinity of the anti-effector cell antibody and the anti-TAA antibody, the type of BiAb (mouse, humanized, or human), the number of binding sites for the T cells or TAA, the presence or absence of decoy antigen, whether the TAA modulates after being engaged by antibody, the type of tumor, the tumor burden, and last, but not least, the amount of 'immunologic' space available for the adoptively transferred cells to expand and function.
用于癌症治疗应用的双特异性抗体（BiAbs）的开发显示出前景。随着我们对触发细胞毒性功能的效应细胞受体生物学的理解不断提高，以及肿瘤相关抗原（TAA）的行为和靶向抗体的结合情况得以阐明，可以设计定制的双特异性抗体试剂，以优化T细胞在体内或体外针对肿瘤的武装。此外，成功进行T细胞免疫治疗的等式中需要考虑的其他变量包括：效应细胞的类型、它们的激活状态、被激活或靶向的效应受体的类型、调节性T细胞（Tregs）的存在、抗效应细胞抗体和抗TAA抗体的亲和力、双特异性抗体的类型（小鼠、人源化或人源）、T细胞或TAA的结合位点数量、诱饵抗原的存在与否、TAA在与抗体结合后是否发生调节、肿瘤的类型、肿瘤负荷，以及最后但同样重要的是，可供过继转移细胞扩增和发挥功能的“免疫”空间量。
