Cogliati T, Brusa P, Canevari S, Caldera M, Mezzanzanica D, Dosio F, Cattel L, Colnaghi M I
Division of Experimental Oncology E, Istituto Nazionale Tumori, Milan, Italy.
Anticancer Res. 1991 Jan-Feb;11(1):417-21.
MOv18, a non-internalizing monoclonal antibody (MAb) with restricted tumor specificity, was conjugated to ricin toxin (RT). According to their ability to bind to galactose residues of Sepharose 6B, the immunoconjugates were fractionated into Bound and Unbound MOv18-RT. The two conjugates could be distinguished by SDS-PAGE, in vivo toxicity and agglutination capability. When the binding activity of both fractions was compared by solid-phase RIA to that of native MAb, it proved to be similar on the relevant target cells but significantly increased on the non relevant cells. On the latter, galactose totally cancelled the binding of the Unbound immunoconjugate, whereas it could only partially reverse that of the Bound MOv18-RT. By in vitro cytotoxic activity, either in the presence or absence of galactose, only a slight selectivity for relevant versus non-relevant target cells was observed for both conjugates. It seems that in the presence of a MAb which is incapable of internalization, the conjugate cytotoxicity could only be attributed to RT, with a loss of the MAb's specificity.
MOv18是一种具有受限肿瘤特异性的非内化单克隆抗体（MAb），它与蓖麻毒素（RT）偶联。根据免疫偶联物与琼脂糖6B半乳糖残基的结合能力，将其分离为结合型和未结合型MOv18-RT。这两种偶联物可通过SDS-PAGE、体内毒性和凝集能力加以区分。当通过固相放射免疫分析（RIA）将这两种组分的结合活性与天然单克隆抗体的结合活性进行比较时，结果表明，在相关靶细胞上二者相似，但在非相关细胞上显著增加。在非相关细胞上，半乳糖完全消除了未结合免疫偶联物的结合，而对于结合型MOv18-RT，半乳糖只能部分逆转其结合。通过体外细胞毒性活性检测，无论有无半乳糖存在，两种偶联物对相关和非相关靶细胞均仅表现出轻微的选择性。似乎在存在无法内化的单克隆抗体的情况下，偶联物的细胞毒性只能归因于蓖麻毒素，单克隆抗体的特异性丧失。
