Advances in HER2-Targeted Cancer Vaccines: From Immunological Basis to Next-Generation Therapeutic Strategies

Biotechnology Department, East China University of Science and Technology, 201424 Shanghai, China

^* Corresponding author: This email address is being protected from spambots. You need JavaScript enabled to view it.

Abstract

HER2-positive breast cancer is aggressive and associated with poor prognosis worldwide. While passive immunotherapy using monoclonal antibodies is effective, resistance and recurrence remain major challenges. HER2-targeted cancer vaccines offer a promising strategy to induce durable, antigen-specific immune responses. This review summarizes the biological and immunological basis of HER2 targeting, including oncogenic signaling and tumor antigenicity, and outlines both passive and active immunotherapeutic approaches. It highlights advances in HER2 vaccines, particularly mRNA-based strategies, and emphasizes combination therapies with immune checkpoint inhibitors, HER2-targeted agents, chemotherapy, and radiotherapy to enhance antitumor immunity and overcome immune evasion. Despite progress, challenges such as low immunogenicity, HLA restriction, and an immunosuppressive tumor microenvironment limit clinical efficacy. Future directions include optimizing antigen design, expanding combination strategies, and leveraging artificial intelligence for personalized vaccine development. Overall, HER2-targeted vaccines represent a promising frontier in next-generation cancer immunotherapy.