Lindvall M, Sjögren H O
Department of Tumor Immunology, Wallenberg Laboratory, University of Lund, Sweden.
Cancer Immunol Immunother. 1991;33(1):21-7. doi: 10.1007/BF01742523.
A monoclonal mouse IgG2b antibody 19F8, directed towards a determinant on the retroviral transmembranous molecule p15E, binds selectively to certain rat tumours, including all tested yolk sac tumours, one rat colon carcinoma, one spontaneous kidney carcinoma and an adenovirus-type-9-induced rat breast tumour, as tested by antibody-dependent cellular cytotoxicity (ADCC) and immunohistochemistry. Groups of rats receiving yolk sac tumour F56 isografts intraperitoneally (i.p.) or subperitoneally (s.p.) were treated with this monoclonal antibody (mAb), 19F8, inoculated twice a week in doses of 100 micrograms. Parallel control groups received analogous inoculations of an isotype-matched monoclonal antibody. A significant growth inhibitory effect was observed with 19F8. In 5/10 rats isografted i.p., tumour outgrowth was completely inhibited and in the other 5 rats the outgrowth was delayed compared to the 10 rats in the control group, which all developed tumours. All rats of the control group developed large volumes of ascites, whereas the 5 rats in the therapy group with eventual tumour outgrowth had little or no ascites. In two experiments with rats carrying subperitoneal isografts and treated with the 19F8 mAb, tumour grew out in 4/5 and 5/10 rats, though growth was delayed compared to the control groups, in which 5/5 and 9/9 rats developed tumours. The tumours grew significantly more slowly in the therapy groups compared to the controls. All rats that developed tumours in the therapy groups showed an anti-idiotypic response against mAb 19F8. The single tumour-free rat in the first experiment and 1/5 tumour-free rats in the other showed no such response. The draining lymph node cells from the tumour-free animals showed a specific proliferative response to yolk sac tumour F56 cells in a mixed lymphocyte tumour cell culture (MLTC), and the MLTC-induced cells were cytotoxic to F56 but not to the natural-killer-sensitive rat T cell lymphoma G1-Tc1. The cytotoxic cell population was more than 90% CD4+. It is concluded that the two test systems for identification of the epitope of p15E detected by mAb 19F8 correlated well in detection of the epitope in the cells (immunohistochemistry) and at the cell surface (ADCC). It is also concluded that mAb 19F8 has a growth-inhibitory effect on yolk sac tumour F56 and that, as a result of the treatment, T cells with specificity for F56 are appearing in draining lymph nodes of tumour-free animals.
一种针对逆转录病毒跨膜分子p15E上某一决定簇的小鼠单克隆IgG2b抗体19F8，通过抗体依赖性细胞毒性（ADCC）和免疫组织化学检测发现，它能选择性地与某些大鼠肿瘤结合，包括所有检测的卵黄囊瘤、一例大鼠结肠癌、一例自发性肾癌以及一株腺病毒9型诱导的大鼠乳腺肿瘤。给腹腔内（i.p.）或腹膜下（s.p.）接种卵黄囊瘤F56同基因移植瘤的大鼠组，用这种单克隆抗体（mAb）19F8进行治疗，每周接种两次，剂量为100微克。平行对照组接受同型匹配单克隆抗体的类似接种。观察到19F8具有显著的生长抑制作用。在腹腔内接种同基因移植瘤的10只大鼠中，5只的肿瘤生长完全被抑制，另外5只的肿瘤生长与对照组的10只大鼠相比有所延迟，对照组的大鼠都长出了肿瘤。对照组的所有大鼠都产生了大量腹水，而最终肿瘤生长的治疗组中的5只大鼠几乎没有或没有腹水。在两项对携带腹膜下移植瘤并用19F8 mAb治疗的大鼠实验中，4/5和5/10的大鼠长出了肿瘤，尽管与对照组相比生长有所延迟，对照组中5/5和9/9的大鼠长出了肿瘤。与对照组相比，治疗组的肿瘤生长明显更慢。治疗组中所有长出肿瘤的大鼠都表现出针对mAb 19F8的抗独特型反应。第一个实验中唯一无肿瘤的大鼠和另一个实验中5只无肿瘤大鼠中的1只没有这种反应。无肿瘤动物的引流淋巴结细胞在混合淋巴细胞肿瘤细胞培养（MLTC）中对卵黄囊瘤F56细胞表现出特异性增殖反应，并且MLTC诱导的细胞对F56具有细胞毒性，但对自然杀伤敏感的大鼠T细胞淋巴瘤G1-Tc1没有细胞毒性。细胞毒性细胞群体中CD4 + 细胞超过90%。得出结论，用于鉴定mAb 19F8所检测的p15E表位的两种测试系统在检测细胞中的表位（免疫组织化学）和细胞表面的表位（ADCC）方面相关性良好。还得出结论，mAb 19F8对卵黄囊瘤F56具有生长抑制作用，并且由于治疗，对F56具有特异性的T细胞出现在无肿瘤动物的引流淋巴结中。
