McCready D R, Balch C M, Fidler I J, Murray J L
Department of General Surgery, University of Texas M. D. Anderson Cancer Center, Houston.
J Natl Cancer Inst. 1989 May 3;81(9):682-7. doi: 10.1093/jnci/81.9.682.
The affinity and specificity of monoclonal antibodies (MAbs) to tumor-associated antigens are often determined by in vitro assays. The specific binding of two anti-human melanoma antibodies (96.5 and ZME-018) and a control antibody (ZCE-025) to three human melanoma cell lines (DX3, A375-M, and Hs294t) was examined under in vitro conditions and compared to in vivo localization of 111In-labeled antibodies to the same cells growing as solid tumors in the subcutis of nude mice. The in vitro binding of the specific MAbs to the tumor cells did not predict in vivo localization. Under in vitro conditions, MAb ZME-018 bound to all three cell lines at levels exceeding that of 96.5, yet ZME-018 did not show superior localization to subcutaneous tumors. MAb 96.5 bound to cultured DX3 cells at levels exceeding those observed with A375-M cells. Yet, 96.5 localized better to A375-M xenografts in nude mice than to DX3 or Hs294t xenografts. Antigen expression differed between in vitro and in vivo growing cells, as evidenced by alteration in binding of 96.5 to tumor cells dissociated from solid subcutaneous tumors. Collectively, the data suggest that in vitro parameters do not predict the clinically relevant localization of MAbs to tumors.
单克隆抗体（MAb）对肿瘤相关抗原的亲和力和特异性通常通过体外试验来确定。在体外条件下检测了两种抗人黑色素瘤抗体（96.5和ZME-018）以及一种对照抗体（ZCE-025）与三种人黑色素瘤细胞系（DX3、A375-M和Hs294t）的特异性结合，并与111In标记的抗体在裸鼠皮下作为实体瘤生长的相同细胞的体内定位进行了比较。特异性单克隆抗体与肿瘤细胞的体外结合并不能预测其体内定位。在体外条件下，单克隆抗体ZME-018与所有三种细胞系的结合水平均超过96.5，但ZME-018对皮下肿瘤的定位并不优于96.5。单克隆抗体96.5与培养的DX3细胞的结合水平超过了A375-M细胞。然而，96.5在裸鼠体内对A375-M异种移植物的定位优于对DX3或Hs294t异种移植物的定位。体外和体内生长的细胞之间抗原表达存在差异，从96.5与从皮下实体瘤分离的肿瘤细胞的结合变化可以看出。总体而言，数据表明体外参数不能预测单克隆抗体在临床上对肿瘤的相关定位。
