Mastellos D C
Protein Chemistry Laboratory, IRRP, National Center for Scientific Research Demokritos, Athens, Greece.
J BUON. 2009 Sep;14 Suppl 1:S123-30.
Complement-based cancer immunotherapy is gaining momentum in recent years due to the growing number of therapeutic anti-tumor antibodies that are receiving approval for clinical trials and are currently used in clinical cancer care. Even though some anti-tumor antibodies have shown moderate therapeutic efficacy, most of them still lag behind, having failed to produce adequately effective responses. The urging need for a therapeutic platform that will enhance both the humoral and cellular effects of antibody treatment prompts the design of more effective combinatorial therapeutics for enhancing complement-mediated tumor cytotoxicity in cancer patients. Cancer cells express or "sequester" host membrane-bound and fluid-phase complement regulators in order to evade complement attack and establish an immunosuppressive microenvironment for tumor growth. Moreover, membrane complement regulators appear to modulate several aspects of T-cell immunity that are relevant to the anti-tumor, adaptive T-cell response. Recently, the concept that complement activation is unfavorable for tumor growth has been drastically challenged by evidence that points to a novel immunomodulatory role of complement in the tumor microenvironment. Taken together, these findings form a new conceptual framework that integrates innate immunity to cancer development. Furthermore, they are anticipated to lead to the rational design of strategies that will exploit innate immune systems, such as complement, in a patient-oriented, "individualized" manner for effective cancer immunotherapy.
近年来，基于补体的癌症免疫疗法发展势头迅猛，这是因为越来越多的治疗性抗肿瘤抗体获得临床试验批准并已应用于临床癌症治疗。尽管一些抗肿瘤抗体已显示出一定的治疗效果，但大多数仍存在不足，未能产生足够有效的反应。迫切需要一个能够增强抗体治疗的体液和细胞效应的治疗平台，这促使人们设计更有效的联合疗法，以增强癌症患者体内补体介导的肿瘤细胞毒性。癌细胞表达或“隔离”宿主膜结合型和液相补体调节因子，以逃避补体攻击，并建立一个有利于肿瘤生长的免疫抑制微环境。此外，膜补体调节因子似乎会调节与抗肿瘤适应性T细胞反应相关的T细胞免疫的多个方面。最近，有证据表明补体激活在肿瘤微环境中具有新的免疫调节作用，这对补体激活不利于肿瘤生长这一概念提出了严峻挑战。综上所述，这些发现形成了一个将先天免疫与癌症发展相结合的新的概念框架。此外，预计它们将促使人们以患者为导向、“个性化”地合理设计利用补体等先天免疫系统的策略，以实现有效的癌症免疫治疗。
