Immunotherapy of malignant disease with tumor antigen-specific monoclonal antibodies.
Immunotherapy of malignant disease with tumor antigen-specific monoclonal antibodies.
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DOI：
10.1158/1078-0432.ccr-09-2345
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发表时间：
2010-01-01
期刊：
影响因子：
--
通讯作者：
Wang X
中科院分区：
文献类型：
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作者：
Campoli M;Ferris R;Ferrone S;Wang X
一些肿瘤抗原（TA）特异性单克隆抗体（mAb）已被FDA批准用于治疗几种主要恶性疾病，并已上市。一旦进入临床，mAb的平均成功率约为30%，并且耐受性良好。这些结果改变了癌症治疗的面貌，使我们更接近更特异、更有效的癌症生物治疗。目前肿瘤免疫学家面临的挑战是确定患者对基于mAb的免疫治疗的差异临床反应的机制。这一信息预计将导致标准的发展，以选择患者接受基于单克隆抗体的免疫治疗。在过去的体外和体内证据表明，TA特异性mAb可以通过诱导肿瘤细胞凋亡、抑制靶向抗原功能、阻断肿瘤细胞信号传导和/或介导补体或细胞依赖性的肿瘤细胞裂解来介导其治疗作用。最近的证据表明，TA特异性mAb可以通过增强树突状细胞（DC）对TA的摄取和T细胞的交叉致敏来诱导TA特异性细胞毒性T细胞应答。在本文中，我们简要总结了已获得FDA批准的TA特异性mAb。接下来，我们回顾了TA特异性mAb治疗效果的潜在机制，重点是TA特异性细胞免疫应答的诱导及其对TA特异性mAb免疫治疗临床疗效的贡献。最后，我们讨论了免疫逃逸机制对基于TA特异性mAb的免疫治疗的临床疗效的潜在负面影响。
A few tumor antigen (TA)-specific monoclonal antibodies (mAb) have been approved by FDA for the treatment of several major malignant diseases and are commercially available. Once in the clinic, mAb have an average success rate of ~30% and are well tolerated. These results have changed the face of cancer therapy, bringing us closer to more specific and more effective biologic therapy of cancer. The challenge facing tumor immunologists at present is represented by the identification of the mechanism(s) underlying patients’ differential clinical response to mAb-based immunotherapy. This information is expected to lead to the development of criteria to select patients to be treated with mAb-based immunotherapy. In the past in vitro and in vivo evidence has shown that TA-specific mAb can mediate their therapeutic effect by inducing tumor cell apoptosis, inhibiting the targeted antigen function, blocking tumor cell signaling and/or mediating complement-or cell-dependent lysis of tumor cells. More recent evidence suggests that TA-specific mAb can induce TA-specific cytotoxic T cell responses by enhancing TA uptake by dendritic cells (DC) and cross-priming of T cells. In this manuscript, we briefly summarize the TA-specific mAb that have received FDA approval. Next we review the potential mechanisms underlying the therapeutic efficacy of TA-specific mAb with emphasis on the induction of TA-specific cellular immune responses and their potential to contribute to the clinical efficacy of TA-specific mAb-based immunotherapy. Lastly, we discuss the potential negative impact of immune escape mechanisms on the clinical efficacy of TA-specific mAb-based immunotherapy.