Ralph P, Nakoinz I
J Leukoc Biol. 1984 Jan;35(1):131-9. doi: 10.1002/jlb.35.1.131.
Six IgG monoclonal antibodies representing the four murine IgG isotypes were active individually in ADCC to T-lymphoma targets mediated by murine macrophages and human blood K cells. The monoclonals were directed against four antigens (Thy-1.2, H-2k, Ly 2.1, Ly 9.2). None was as effective in ADCC as allo-anti-Thy-1.2 serum or rabbit anti-mouse spleen serum, even at plateau levels of killing. Monoclonals gave the highest levels of ADCC at relatively low amounts of antibody bound to targets; increasing the amount of bound antibody by 10- to 100-fold did not increase murine macrophage-mediated cytotoxicity. In contrast, ADCC using alloantiserum continued to increase over the same range of antibody bound to the tumor targets. The activity of individual monoclonals was not enhanced by the presence of various dilutions of normal mouse or rabbit serum, suggesting that the superiority of the allo- and hetero-antisera was due to their content of heterogeneous antibodies. IgG monoclonals of different isotypes and recognizing different antigens gave enhanced ADCC in combination; monoclonals to the same antigen did not. An IgM anti-Thy-1.2 monoclonal was inactive in ADCC and inhibited the activity of IgG monoclonals of the same specificity. These studies show that IgG antibodies of different specificity and class can collaborate in ADCC, and that this cooperative effect is not due simply to increased amounts of antibody bound to the tumor targets.
代表四种鼠源IgG同种型的六种IgG单克隆抗体，在由鼠巨噬细胞和人血K细胞介导的针对T淋巴瘤靶标的ADCC中各自具有活性。这些单克隆抗体针对四种抗原（Thy-1.2、H-2k、Ly 2.1、Ly 9.2）。即使在杀伤的平台水平，也没有一种单克隆抗体在ADCC中像同种异体抗Thy-1.2血清或兔抗鼠脾血清那样有效。单克隆抗体在与靶标结合的抗体量相对较低时能产生最高水平的ADCC；将结合抗体的量增加10至100倍并不会增加鼠巨噬细胞介导的细胞毒性。相比之下，使用同种异体抗血清的ADCC在与肿瘤靶标结合的相同抗体范围内持续增加。正常小鼠或兔血清的各种稀释液的存在并未增强单个单克隆抗体的活性，这表明同种异体和异种抗血清的优越性归因于它们所含的异质性抗体。识别不同抗原的不同同种型的IgG单克隆抗体联合使用时能增强ADCC；针对相同抗原的单克隆抗体则不能。一种IgM抗Thy-1.2单克隆抗体在ADCC中无活性，并抑制相同特异性的IgG单克隆抗体的活性。这些研究表明，不同特异性和类别的IgG抗体可以在ADCC中协同作用，并且这种协同效应并非仅仅由于与肿瘤靶标结合的抗体量增加所致。
