Molthoff C F, Pinedo H M, Schlüper H M, Nijman H W, Boven E
Department of Oncology, Free University Hospital, Amsterdam, The Netherlands.
Br J Cancer. 1992 May;65(5):677-83. doi: 10.1038/bjc.1992.144.
Monoclonal antibody (MAb) 139H2 was previously shown to localise specifically into ovarian cancer xenografts in nude mice. MAb 139H2 was compared with MAbs OC125 and OV-TL 3, all reactive with ovarian carcinomas, for the binding characteristics as IgG and F(ab')2 fragments with the use of the OVCAR-3 cell line grown in vitro and as s.c. xenografts. Immunoperoxidase staining of OVCAR-3 tissue sections with MAbs OC125 and 139H2 was heterogeneous, whereas MAb OV-TL 3 showed homogeneity. No differences in binding were observed between IgG and F(ab')2. The avidity expressed as apparent affinity constants of MAbs OC125, OV-TL 3 and 139H2 for OVAR-3 cells were 1 x 10(9) M-1, 1 x 10(9) M-1, and 1 x 10(8) M-1, while the number of antigenic determinants were 5 x 10(6), 1 x 10(6) and 7 x 10(6), respectively. In OVCAR-3 bearing nude mice the blood half-lives of the MAbs as IgG and F(ab')2 were approximately 50 h and 6 h, respectively. Maximum tumour uptake for the whole MAbs OC125, OV-TL 3, 139H2 and a control MAb 2C7 was 8.5%, 17.7%, 11.1% and 2.5% of the injected dose g-1, reached at 72 h after injection. For the respective F(ab')2 fragments, the maximum values were 5.2%, 10.0%, 5.5% and 1.9% of the injected dose g-1, reached between 6 h and 15 h. Tumour to non-tumour ratios were more favourable for the F(ab')2 fragments as compared to those for MAbs as IgG. Biodistribution in mice bearing a control tumour confirmed the specificity of tumour localisation of MAbs OC125, OV-TL 3 and 139H2. After injection of a tracer dose of 10 microCi of radiolabelled MAbs OC125, OV-TL 3 and 139H2 as IgG, tumours received 38 cGy, and 9 cGy. In our OVCAR-3 model, a ranking in efficiency in tumour localisation would indicate MAb OV-TL 3 as most favourable MAb, but cross-reactivity with subpopulations of human white blood cells might hamper its clinical use. Dosimetric data indicate a 4-fold higher radiation absorbed dose to tumours for IgG compared with F(ab')2 fragments.
单克隆抗体（MAb）139H2先前已被证明可特异性定位于裸鼠的卵巢癌异种移植瘤中。将MAb 139H2与MAbs OC125和OV-TL 3进行比较，这三种抗体均与卵巢癌反应，利用体外培养的OVCAR-3细胞系以及皮下异种移植瘤，研究它们作为IgG和F(ab')2片段的结合特性。用MAbs OC125和139H2对OVCAR-3组织切片进行免疫过氧化物酶染色呈异质性，而MAb OV-TL 3呈同质性。未观察到IgG和F(ab')2之间结合的差异。MAbs OC125、OV-TL 3和139H2对OVAR-3细胞的亲和力以表观亲和常数表示分别为1×10⁹ M⁻¹、1×10⁹ M⁻¹和1×10⁸ M⁻¹，而抗原决定簇的数量分别为5×10⁶、1×10⁶和7×10⁶。在携带OVCAR-3的裸鼠中，MAbs作为IgG和F(ab')2的血液半衰期分别约为50小时和6小时。MAbs OC125、OV-TL 3、139H2和对照单克隆抗体2C7的整个抗体的最大肿瘤摄取量分别为注射剂量的8.5%、17.7%、11.1%和2.5% g⁻¹，在注射后72小时达到。对于各自的F(ab')2片段，最大值分别为注射剂量的5.2%、10.0%、5.5%和1.9% g⁻¹，在6小时至15小时之间达到。与作为IgG的MAbs相比，F(ab')2片段的肿瘤与非肿瘤比值更有利。在携带对照肿瘤的小鼠中的生物分布证实了MAbs OC125、OV-TL 3和139H2肿瘤定位的特异性。注射10微居里放射性标记的MAbs OC125、OV-TL 3和139H2作为IgG的示踪剂量后，肿瘤接受的辐射剂量分别为38 cGy和9 cGy。在我们的OVCAR-3模型中，肿瘤定位效率的排名表明MAb OV-TL 3是最有利的单克隆抗体，但与人白细胞亚群的交叉反应性可能会妨碍其临床应用。剂量学数据表明，与F(ab')2片段相比，IgG对肿瘤的辐射吸收剂量高4倍。
