Porter L E, Nelson H, Ethem Gecim I, Rice D C, Thibault C, Chapoval A I
Department of Surgery, Mayo Clinic and Foundation, Rochester, MN 55905, USA.
Cancer Immunol Immunother. 1997 Nov-Dec;45(3-4):180-3. doi: 10.1007/s002620050427.
The aim of this work was to test for cure and immunity in a micrometastatic tumor model using in vivo T cell activation with staphylococcal enterotoxin B (SEB) and retargeting with antitumor x anti-CD3 F(ab')2 bispecific antibodies (bsAb). All studies were performed in C3H/HeN mice using syngeneic tumor cell lines. For survival studies, mice were injected intravenously on day 0 with CL62 (a p97-transfected clone of the K1735 murine melanoma tumor). Day-3 treatments included saline (control), SEB (50 gamma g intraperitoneal) with or without bsAb (5 micrograms i.v.). Cured mice, surviving beyond 60 days, were rechallenged with subcutaneous CL62, K1735, or a nonmelanoma control, AG104. SEB activation studies were performed with pulmonary tumor-infiltrating lymphocytes isolated from 10-day established CL62 tumors. Maximal tumor-infiltrating lymphocyte cytotoxicity was demonstrated 24 h following SEB injection, therefore bsAb treatments were administered 24 h after SEB. When survival was examined at 60 days, there were significantly more survivors in the group receiving SEB plus bsAb (70%) compared to the group receiving SEB alone (30%), and the controls (0%) (P = 0.02 and P < 0.01, respectively). Mice cured of CL62 using SEB alone or with bsAb demonstrated equal immunity to CL62, however, mice treated with SEB plus bsAb were more often immune to the p97-parental cell line, K1735(P = 0.001). Ag104 consistently grew in all mice. Results of these studies demonstrate that SEB plus bsAb can be effective, not only in curing tumors but also in providing protective immunity against targeted and non-targeted tumor antigens.
本研究旨在利用葡萄球菌肠毒素B（SEB）进行体内T细胞激活，并使用抗肿瘤x抗CD3 F(ab')2双特异性抗体（bsAb）进行重定向，在微转移肿瘤模型中测试治愈和免疫效果。所有研究均在C3H/HeN小鼠中使用同基因肿瘤细胞系进行。对于生存研究，在第0天给小鼠静脉注射CL62（K1735鼠黑色素瘤肿瘤的p97转染克隆）。第3天的治疗包括生理盐水（对照）、SEB（50微克腹腔注射），加或不加bsAb（5微克静脉注射）。存活超过60天的治愈小鼠，用皮下注射CL62、K1735或非黑色素瘤对照AG104进行再次攻击。SEB激活研究是用从建立10天的CL62肿瘤中分离的肺肿瘤浸润淋巴细胞进行的。SEB注射后24小时显示出最大的肿瘤浸润淋巴细胞细胞毒性，因此bsAb治疗在SEB注射后24小时进行。当在60天时检查生存率时，接受SEB加bsAb的组（70%）的存活者明显多于单独接受SEB的组（30%）和对照组（0%）（P分别为0.02和P<0.01）。单独使用SEB或与bsAb一起治愈CL62的小鼠对CL62表现出同等的免疫力，然而，用SEB加bsAb治疗的小鼠对p97亲本细胞系K1735更常具有免疫力（P = 0.001）。Ag104在所有小鼠中均持续生长。这些研究结果表明，SEB加bsAb不仅可有效治愈肿瘤，还可提供针对靶向和非靶向肿瘤抗原的保护性免疫。
