Clinical progress in the field of HER2-positive breast cancer therapy has been dramatically improved by understanding of the immune regulatory mechanisms of tumor microenvironment. Passive immunotherapy utilizing recombinant monoclonal antibodies (mAbs), particularly trastuzumab and pertuzumab has proved to be an effective strategy in HER2-positive breast cancer treatment. However, resistance to mAb therapy and relapse of disease are still considered important challenges in clinical practice. There are increasing reports on the induction of cellular and humoral immune responses in HER2-positive breast cancer patients. More recently, increasing efforts are focused on using HER2-derived peptide vaccines for active immunotherapy. Here, we discuss the development of various HER2-derived vaccines tested in animal models and human clinical trials. Different formulations and strategies to improve immunogenicity of the antigens in animal studies are also discussed. Furthermore, other immunotherapeutic approaches to HER2 breast cancer including, CTLA-4 inhibitors, immune checkpoint inhibitors, anti PD-1/PD-L1 antibodies are presented.

中文翻译：

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HER2阳性乳腺癌免疫治疗：疫苗开发的重点。

通过了解肿瘤微环境的免疫调节机制，HER2阳性乳腺癌治疗领域的临床进展得到了显着改善。利用重组单克隆抗体（mAb），特别是曲妥珠单抗和帕妥珠单抗的被动免疫疗法已被证明是治疗HER2阳性乳腺癌的有效策略。然而，在临床实践中，仍然认为对mAb疗法的抗性和疾病的复发是重要的挑战。关于在HER2阳性乳腺癌患者中诱导细胞和体液免疫反应的报道不断增加。最近，越来越多的努力集中在使用源自HER2的肽疫苗进行主动免疫治疗上。在这里，我们讨论在动物模型和人类临床试验中测试的各种HER2衍生疫苗的开发。还讨论了在动物研究中提高抗原免疫原性的不同配方和策略。此外，还提出了其他针对HER2乳腺癌的免疫治疗方法，包括CTLA-4抑制剂，免疫检查点抑制剂，抗PD-1 / PD-L1抗体。