Nimmerjahn Falk, Ravetch Jeffrey V
Division of Genetics, Department of Biology, University of Erlangen-Nuremberg, Erlangen, Germany.
Cancer Immun. 2012;12:13. Epub 2012 May 1.
Monoclonal antibodies of the immunoglobulin G (IgG) isotype have become a well-established therapeutic tool for the targeting of malignant cells in tumor patients. Despite tremendous success in the treatment of lymphoma and breast cancer, it has also become clear that we may not be able to further improve antibody therapy of cancer by simply generating more tumor-specific antibodies with a higher affinity. Instead, the work of many groups in the past years suggests that optimizing the recruitment of effector functions provided by the adaptive and innate immune systems via engineering of the IgG constant domain may hold great promise to achieve enhanced therapeutic activities. A major goal in cancer therapy would be to initiate adaptive immune responses to the patient's tumor that would result in long-term protection against recurrence. The use of immunostimulatory antibodies shows great promise in stimulating adaptive immune responses. Surprisingly, recent studies also implicate an important role for the antibody constant domain in the activity of these molecules in vivo, opening up new possibilities to further improve the activity of immunomodulatory antibodies by Fc engineering.
免疫球蛋白G（IgG）同种型的单克隆抗体已成为肿瘤患者靶向恶性细胞的成熟治疗工具。尽管在淋巴瘤和乳腺癌治疗方面取得了巨大成功，但也很明显，我们可能无法通过简单地产生更多具有更高亲和力的肿瘤特异性抗体来进一步改善癌症抗体治疗。相反，过去几年许多研究小组的工作表明，通过IgG恒定区工程优化适应性和先天性免疫系统提供的效应功能的募集，有望实现增强的治疗活性。癌症治疗的一个主要目标是引发针对患者肿瘤的适应性免疫反应，从而实现长期预防复发。使用免疫刺激抗体在刺激适应性免疫反应方面显示出巨大潜力。令人惊讶的是，最近的研究还表明抗体恒定区在这些分子的体内活性中起着重要作用，这为通过Fc工程进一步改善免疫调节抗体的活性开辟了新的可能性。
