抗体介导的吞噬作用在癌症免疫治疗中的作用。
Antibody-mediated phagocytosis in cancer immunotherapy.
机构信息
Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, Virginia, USA.
Beirne B. Carter Center for Immunology Research, University of Virginia, Charlottesville, Virginia, USA.
出版信息
Immunol Rev. 2023 Oct;319(1):128-141. doi: 10.1111/imr.13265. Epub 2023 Aug 21.
Unconjugated monoclonal antibodies (mAb) have revolutionized the treatment of many types of cancer. Some of these mAbs promote the clearance of malignant cells via direct cytotoxic effects. More recently, antibody-dependent cellular phagocytosis (ADCP) has been appreciated as a major mechanism of action for a number of widely-used mAbs, including anti-CD20 (rituximab, obinutuzumab), anti-HER2 (trazituzumab), and anti-CD38 (daratumumab). However, as a monotherapy these ADCP-inducing mAbs produce insufficient levels of cytotoxicity in vivo and are not curative. As a result, these mAbs are most effectively used in combination therapies. The efficacy of these mAbs is further hampered by the apparent development of drug resistance by many patients. Here we will explore the role of ADCP in cancer immunotherapy and discuss the key factors that could limit the efficacy of ADCP-inducing mAbs in vivo. Finally, we will discuss current insights and approaches being applied to overcome these limitations.
未结合的单克隆抗体 (mAb) 彻底改变了许多类型癌症的治疗方法。其中一些 mAb 通过直接细胞毒性作用促进清除恶性细胞。最近，抗体依赖性细胞吞噬作用 (ADCP) 已被认为是许多广泛使用的 mAb 的主要作用机制，包括抗 CD20（利妥昔单抗、奥滨尤妥珠单抗）、抗 HER2（曲妥珠单抗）和抗 CD38（达雷妥尤单抗）。然而，作为单一疗法，这些诱导 ADCP 的 mAb 在体内产生的细胞毒性水平不足，并且无法治愈。因此，这些 mAb 最有效地用于联合治疗。这些 mAb 的疗效进一步受到许多患者明显出现药物耐药性的阻碍。在这里，我们将探讨 ADCP 在癌症免疫治疗中的作用，并讨论可能限制体内诱导 ADCP 的 mAb 疗效的关键因素。最后，我们将讨论目前正在应用的克服这些限制的见解和方法。
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