Ochi A, Migita K, Xu J, Siminovitch K
Department of Immunology, University of Toronto, Ontario, Canada.
J Immunol. 1993 Sep 15;151(6):3180-6.
We have investigated the in vivo efficacy of Staphylococcus aureus enterotoxin B (SEB) coupled to tumor-specific anti-idiotypic antibody in redirecting T cell effector activity to the growth inhibition of B lymphoma 38C13. Incubation of 38C13 lymphoma cells with syngeneic C3H/He splenic cells and SEB-anti-Id conjugate was associated with between 80 and 100% growth inhibition of the tumor cells. V beta 8+ T cells were integral for the SEB-anti-Id-induced tumor cell growth inhibition. Administration of SEB-anti-Id i.v. to mice previously inoculated with 38C13 lymphoma cells led to greater than 40% survival at 100 days compared to a mean survival of 21 days in control animals. When we compared this reagent with other targeting constructs--the anti-CD3-anti-Id and anti-TCR V beta 8-anti-Id--these more or less effectively prevented tumor growth. However, anti-CD3-anti-Id impaired almost the entire T cell response, whereas the effects of SEB-anti-Id or anti-V beta 8-anti-Id had effects limited to V beta 8+ T cells. Previous studies showed that in vivo administration of SEB caused a small change in V beta 8+ T cell numbers in contrast to anti-V beta 8 antibody, which depleted the entire population. These results together suggest that SEB-anti-tumor antibody conjugates represent a potentially powerful approach for better tumor immunotherapy.
我们研究了与肿瘤特异性抗独特型抗体偶联的金黄色葡萄球菌肠毒素B（SEB）在将T细胞效应活性重定向至抑制B淋巴瘤38C13生长方面的体内疗效。38C13淋巴瘤细胞与同基因C3H/He脾细胞及SEB-抗独特型抗体偶联物共同孵育，可使肿瘤细胞生长抑制率达80%至100%。Vβ8 + T细胞对于SEB-抗独特型抗体诱导的肿瘤细胞生长抑制至关重要。给预先接种38C13淋巴瘤细胞的小鼠静脉注射SEB-抗独特型抗体，100天时生存率大于40%，而对照动物的平均生存期为21天。当我们将该试剂与其他靶向构建体——抗CD3-抗独特型抗体和抗TCR Vβ8-抗独特型抗体——进行比较时，它们或多或少能有效阻止肿瘤生长。然而，抗CD3-抗独特型抗体几乎损害了整个T细胞反应，而SEB-抗独特型抗体或抗Vβ8-抗独特型抗体的作用仅限于Vβ8 + T细胞。先前的研究表明，与抗Vβ8抗体使整个Vβ8 + T细胞群体耗竭不同，体内给予SEB会使Vβ8 + T细胞数量发生微小变化。这些结果共同表明，SEB-抗肿瘤抗体偶联物代表了一种潜在的强大方法，有望实现更好的肿瘤免疫治疗。
