肿瘤细胞治疗研究
英文原题：Targeting ADCC: A different approach to HER2 breast cancer in the immunotherapy era.
Targeting ADCC: A different approach to HER2 breast cancer in the immunotherapy era.
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随着抗HER2靶向疗法的发展，HER2扩增型乳腺癌患者的临床结局已有改善，但患者仍可能在根治性治疗后复发，或在转移阶段出现进展。在免疫疗法不断发展的当下，人们对抗HER2抗体所诱导的针对HER2肿瘤细胞的免疫应答有了迅速深入的认识。曲妥珠单抗可激活HER2过表达乳腺癌患者的自然杀伤（NK）细胞，提示短期曲妥珠单抗单药治疗的疗效，除了直接抑制HER2外，也可能与抗体依赖性细胞介导的细胞毒作用（ADCC）有关。目前，早期和晚期疾病的标准治疗均为曲妥珠单抗联合帕妥珠单抗双重阻断HER2，因为这一组合可能产生叠加的ADCC效应。对于复发或进展患者，FcγRIIIa多态性及免疫抑制环境等因素可能削弱ADCC。因此，研究者正在探索新药开发策略，以增强抗HER2治疗诱导的ADCC应答。本文综述通过单克隆抗体工程改造和联合治疗增强ADCC的策略及其依据，并重点介绍临床结果和正在进行的试验。
The clinical outcome of patients with human epidermal growth factor receptor 2 (HER2) amplified breast carcinoma (BC) has improved with the development of anti-HER2 targeted therapies.
However, patients can experience disease recurrence after curative intent and disease progression in the metastatic setting. In the current era of evolving immunotherapy agents, the understanding of the immune response against HER2 tumor cells developed by anti-HER2 antibodies (Abs) is rapidly evolving. Trastuzumab therapy promotes Natural Killer (NK) cell activation in patients with BC overexpressing HER2, indicating that the efficacy of short-term trastuzumab monotherapy, albeit direct inhibition of HER, could also be related with antibody-dependent cell-mediated cytotoxicity (ADCC).
Currently, dual HER2 blockade using trastuzumab and pertuzumab is the standard of care in early and advanced disease as this combination could confer an additive effect in ADCC. In patients with disease relapse or progression, ADCC may be hampered by several factors such as Fc RIIIa polymorphism and an immunosuppressive environment, among others.
Hence, new drug development strategies are being investigated aiming to boost the ADCC response triggered by anti-HER2 therapy. In this review, we summarize these strategies and the rationale, through mAbs engineering and combinatorial strategies, focusing on clinical results and ongoing trials.
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