用于直接抗肿瘤治疗以及将各种治疗剂系统性递送至癌细胞的基因工程抗体。
Genetically engineered antibodies for direct antineoplastic treatment and systematic delivery of various therapeutic agents to cancer cells.
作者信息
Bodey B
机构信息
Department of Pathology, School of Medicine, University of Southern California & Department of Pediatrics, Division of Hematology and Oncology, Childrens Hospital, Los Angeles, Los Angeles, CA, USA.
出版信息
Expert Opin Biol Ther. 2001 Jul;1(4):603-17. doi: 10.1517/14712598.1.4.603.
Classical antineoplastic therapeutic modalities such as surgery, radiation, and chemotherapy not only fail to cure the great majority of neoplasms, but their employment often leads to severe and debilitating side effects associated with severe neoplasm-related morbidity. Immunotherapy as a fourth modality of anti-cancer therapy has already been proven to be quite effective. The astonishing immunophenotypic (IP) heterogeneity of neoplastic cells, the different cytotoxic activity associated with the moiety linked to given monoclonal antibodies (mAb), and mostly the impressive genetic modulation capabilities of cancer cells still remain as yet unsolved difficulties in the present immunotherapy of human neoplasms. The advances in mAb production have revitalised the initial concept of use of cancer cell specific "magic bullets." Antibodies represent new approaches to anti-cancer therapy: they are neoplastic cell-specific and lethal to neoplastically transformed cells via immune effector mechanisms with no toxicity to normal tissues. They are being observed and developed, adhering to the old prayer: "Destroy the diseased tissues, preserve the normal." Strategies for the employment of antibodies include: 1) immune reaction directed destruction of neoplastic cells; 2) interference with the growth and differentiation of malignant cells; 3) antigen epitope directed transport of anti-cancer agents to neoplastic cells; 4) anti-idiotype tumour vaccines; and 5) development of engineered (humanized) mouse mAbs for anticancer therapy. In addition, a variety of agents (e.g. toxins, radionuclides, chemotherapeutic drugs) have been conjugated to mouse and human mAbs for selective delivery to neoplastic cells.
传统的抗肿瘤治疗方式,如手术、放疗和化疗,不仅无法治愈绝大多数肿瘤,而且其应用往往会导致严重且使人虚弱的副作用,以及与肿瘤相关的严重发病率。免疫疗法作为抗癌治疗的第四种方式,已被证明相当有效。肿瘤细胞惊人的免疫表型(IP)异质性、与特定单克隆抗体(mAb)连接部分相关的不同细胞毒性活性,以及最重要的是癌细胞令人印象深刻的基因调控能力,在目前人类肿瘤免疫治疗中仍然是尚未解决的难题。单克隆抗体生产的进展使癌细胞特异性“魔弹”的最初概念得以复兴。抗体代表了抗癌治疗的新方法:它们对肿瘤细胞具有特异性,通过免疫效应机制对肿瘤转化细胞具有致死性,而对正常组织无毒性。它们正按照古老的祈愿被观察和开发:“摧毁患病组织,保留正常组织。”抗体的应用策略包括:1)通过免疫反应直接破坏肿瘤细胞;2)干扰恶性细胞的生长和分化;3)将抗癌药物定向运输到肿瘤细胞;4)抗独特型肿瘤疫苗;5)开发用于抗癌治疗的工程化(人源化)小鼠单克隆抗体。此外,多种药物(如毒素、放射性核素、化疗药物)已与小鼠和人单克隆抗体偶联,用于选择性地递送至肿瘤细胞。