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

• Published in: Cancers 2022-11, Vol.14 (22), p.5678
• Main Authors: Tobias, Joshua, Drinić, Mirjana, Schmid, Anna, Hladik, Anastasiya, Watzenböck, Martin L, Battin, Claire, Garner-Spitzer, Erika, Steinberger, Peter, Kundi, Michael, Knapp, Sylvia, Zielinski, Christoph C, Wiedermann, Ursula
• Format: Article
• Language: English
• Subjects: Antigen (tumor-associated); Antigens; Apoptosis; B cells; Biological products; Breast cancer; Cancer; Cancer therapies; Cancer vaccines; Care and treatment; Chemotherapy; Clinical trials; Cytotoxicity; Dosage and administration; Epitopes; ErbB-2 protein; Health aspects; Immune checkpoint; Immune checkpoint inhibitors; Immune system; Immunological memory; Immunotherapy; Kinases; Ligands; Lymphocytes; Medical prognosis; Metastasis; Monoclonal antibodies; PD-1 protein; PD-L1 protein; Peptides; Review; T cell receptors; Tumors
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers14225678

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.