Hurwitz E, Burowski D, Kashi R, Hollander N, Haimovich J
Int J Cancer. 1986 May 15;37(5):739-45. doi: 10.1002/ijc.2910370515.
Antibodies directed against idiotypic determinants of the cell-surface IgM of a B lymphoma, 38c, were effective in delaying development of the tumor and in some instances in preventing its growth. The efficacity of the anti-idiotype antibodies was markedly increased when they were injected in combination with anti-neoplastic drugs. Since chemotherapy, as such, is limited by the general toxicity of the drugs it was of advantage to apply them in low doses. The drug doses used were mostly ineffective by themselves, yet were active in combination with the antibody in a more than additive fashion. We performed studies designed to elucidate the mechanism of the synergy between the anti-idiotype antibodies and the drugs. The data suggest that the activity of the antibody is partly indirect and is mediated through the host's effector cells. In the case of one drug, daunomycin, the activity is also, at least in part, mediated through peritoneal exudate cells (PEC). Daunomycin injected intraperitoneally activated PEC. Such activated PEC, when injected into recipient mice, could replace the drug in its synergy with the antibody. In conclusion, it was shown that it is possible to increase the effectiveness either of antibodies to tumor cells or of cytotoxic drugs by combination therapy.
针对B淋巴瘤38c细胞表面IgM独特型决定簇的抗体，在延缓肿瘤发展以及在某些情况下阻止其生长方面具有效果。当抗独特型抗体与抗肿瘤药物联合注射时，其效力显著增强。由于化疗本身受药物总体毒性的限制，以低剂量应用这些药物是有利的。所使用的药物剂量本身大多无效，但与抗体联合时却以超相加的方式发挥作用。我们进行了旨在阐明抗独特型抗体与药物之间协同作用机制的研究。数据表明，抗体的活性部分是间接的，并且是通过宿主的效应细胞介导的。就一种药物柔红霉素而言，其活性至少部分也是通过腹腔渗出细胞（PEC）介导的。腹腔注射柔红霉素可激活PEC。这种激活的PEC，当注射到受体小鼠体内时，在与抗体的协同作用中可以替代药物。总之，研究表明联合治疗有可能提高针对肿瘤细胞的抗体或细胞毒性药物的有效性。
