Division of Surgical Oncology, North Shore Univ. Hospital, Manhasset, NY 11030, USA.
Curr Drug Deliv. 2012 Jan;9(1):52-6. doi: 10.2174/156720112798376087.
Tumor associated antigens from pooled allogeneic membrane proteins were isolated, partially purified and tested as a possible vaccine in patients with stage II and III colon cancer. The vaccine, when given in combination with an adjuvant following surgical resection, resulted in marked improvement in survival compared to control patients having only undergone surgical resection of their tumor. While it was possible to demonstrate that patients receiving vaccine turned on both humoral and cell mediated responses, it appears that survivors remaining free of disease at 5-7 yrs post op were able to mount a strong IgG1 response as the primary mechanism for tumor destruction. Antibodies from hybridomas made against the vaccines resulted in production of monoclonals with a high degree of ADCC. Those monoclonals targeting pancreatic cancer and in particular the MUC5ac mutated antigen representing tumor immunogen were studied in detail. Animal models indicated rapid tumor destruction when nude mice, injected with human pancreatic cancer were then immunized with NPC-1 monoclonal antibody targeting mutated MUC5ac. FDA studies including tissue cross reactivity, biodistribution, and cytokine release assays indicated safety and efficacy of the monoclonals we have developed. Submission of the IND allowed for initiation of the Phase I trial using mAb NPC-1 targeting pancreatic cancer when that antigen was found to be expressed.
从同种异体膜蛋白的混合肿瘤相关抗原中分离、部分纯化并测试作为 II 期和 III 期结肠癌患者的可能疫苗。与仅接受肿瘤切除术的对照患者相比，手术后给予疫苗联合佐剂可显著提高患者的生存率。虽然可以证明接受疫苗的患者既产生了体液又产生了细胞介导的反应，但似乎在手术后 5-7 年无疾病存活的幸存者能够产生强烈的 IgG1 反应作为肿瘤破坏的主要机制。针对疫苗产生的杂交瘤抗体导致产生具有高 ADCC 活性的单克隆抗体。针对胰腺肿瘤，特别是针对代表肿瘤免疫原的 MUC5ac 突变抗原的单克隆抗体进行了详细研究。动物模型表明，当用靶向突变 MUC5ac 的 NPC-1 单克隆抗体免疫注射人胰腺癌细胞的裸鼠时，肿瘤迅速破坏。包括组织交叉反应、生物分布和细胞因子释放测定在内的 FDA 研究表明，我们开发的单克隆抗体具有安全性和疗效。当发现表达抗原时，提交 IND 允许使用靶向胰腺肿瘤的 mAb NPC-1 开始进行 I 期试验。
