Combined Vaccination with B Cell Peptides Targeting Her-2/neu and Immune Checkpoints as Emerging Treatment Option in Cancer

SIMPLE SUMMARY: Therapies with monoclonal antibodies (mAbs) targeting tumor-associated antigens (TAAs) or immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment. Nevertheless, the inevitable development of resistance and the failure to respond are among this approach’s disadvantages, limiting the duration of disease- or progression-free and overall survival. As an alternative to therapeutically efficacious monoclonal antibodies, the concept of active immunization with vaccines has been repeatedly discussed. In particular, mimotopes, representing the B cell epitope of therapeutic mAbs, have been shown to induce immunological memory and effectively produce antibodies with similar functionality to the respective mAbs/ICIs. This review focuses on a new frontier of vaccinations directed against two cancer-relevant targets, addresses concerns about the safety of active immunization targeting PD-1 and discusses limitations and outlooks. ABSTRACT: The application of monoclonal antibodies (mAbs), targeting tumor-associated (TAAs) or tumor-specific antigens or immune checkpoints (ICs), has shown tremendous success in cancer therapy. However, the application of mAbs suffers from a series of limitations, including the necessity of frequent administration, the limited duration of clinical response and the emergence of frequently pronounced immune-related adverse events. However, the introduction of mAbs has also resulted in a multitude of novel developments for the treatment of cancers, including vaccinations against various tumor cell-associated epitopes. Here, we reviewed recent clinical trials involving combination therapies with mAbs targeting the PD-1/PD-L1 axis and Her-2/neu, which was chosen as a paradigm for a clinically highly relevant TAA. Our recent findings from murine immunizations against the PD-1 pathway and Her-2/neu with peptides representing the mimotopes/B cell peptides of therapeutic antibodies targeting these molecules are an important focus of the present review. Moreover, concerns regarding the safety of vaccination approaches targeting PD-1, in the context of the continuing immune response, as a result of induced immunological memory, are also addressed. Hence, we describe a new frontier of cancer treatment by active immunization using combined mimotopes/B cell peptides aimed at various targets relevant to cancer biology.