Renner C, Pfreundschuh M
Medical Department I, University of the Saarland, Homburg, Germany.
J Hematother. 1995 Oct;4(5):447-51. doi: 10.1089/scd.1.1995.4.447.
To test the feasibility and efficacy of a new immunotherapeutic approach in Hodgkin's disease, bispecific monoclonal antibodies (BsmAb) were established with specificity for the Hodgkin's-associated CD30 antigen and for CD16 (on NK cells) or CD3 and CD28 (on T lymphocytes), respectively. These BsmAb induced a specific and efficient NK cell or T cell-mediated cytotoxicity in vitro. The treatment of severe combined immunodeficiency (SCID) mice with the NK (anti-CD16/CD30) or T cell (anti-CD3/CD30 and anti-CD28/CD30) activating BsmAb followed by administration of resting human lymphocytes led to complete remission of established heterotransplanted human Hodgkin's tumors. Even disseminated tumors were cured. Studies on the mechanism responsible for tumor destruction revealed that treatment efficacy depended on lymphocyte activation at the tumor site. Localization of human lymphocytes in mice was BsmAb mediated and antigen specific as activated lymphocytes were only detected in CD30+ tumors but not in CD30- colorectal carcinomas co-established as a control in the same animal.
为了测试一种新的免疫治疗方法在霍奇金病中的可行性和疗效，分别制备了对霍奇金相关CD30抗原以及对CD16（自然杀伤细胞上）或CD3和CD28（T淋巴细胞上）具有特异性的双特异性单克隆抗体（BsmAb）。这些BsmAb在体外诱导了特异性且高效的自然杀伤细胞或T细胞介导的细胞毒性。用激活自然杀伤细胞（抗CD16/CD30）或T细胞（抗CD3/CD30和抗CD28/CD30）的BsmAb治疗严重联合免疫缺陷（SCID）小鼠，随后给予静息的人淋巴细胞，可使已建立的异种移植人霍奇金肿瘤完全缓解。即使是播散性肿瘤也能被治愈。对肿瘤破坏机制的研究表明，治疗效果取决于肿瘤部位的淋巴细胞激活。人淋巴细胞在小鼠体内的定位是由BsmAb介导且具有抗原特异性的，因为仅在CD30+肿瘤中检测到激活的淋巴细胞，而在同一动物中作为对照共同建立的CD30-结肠直肠癌中未检测到。
