2018 Volume 25 Issue 1 Pages 40-49
Tumor cells commonly express several immunogenic antigens, such as tumor-associated antigens (TAAs) that can be recognized as foreign antigens by the immune system and elicit anti-tumor immune responses in cancer patients. Recently it was reported by many researchers that mutated peptides derived from cancer-associated non-synonimous single nucleotide variants (SNVs), so called “Neo antigenic peptides”, can induce strong anti-tumor immune responses in both CTLs and Th cells in tumor-bearing mice and cancer patients. These TAAs or neoantigens expressed in cancer cells have been identified and utilized as targets for cancer immunotherapy. One approach to elicit tumor-specific immune responses is termed peptide-based cancer vaccination; it involves administration of TAAs or neoantigen-derived peptide for treatment of cancers. There have been several forms of peptide-based cancer vaccines depending on which effector cells, such as CTLs or CD4+ T-helper cells, are targeted to be activated. Many phase I and II clinical trials of peptide-based cancer vaccines using TAA-derived CTL epitopes (short peptides), T-helper cell epitopes (long peptides) or dendritic cells (DCs) loaded with TAA-derived short or long peptides for various malignant tumors have been conducted and provide clinical benefits in a small fraction of patients. Although peptide-based cancer vaccines have sometimes shown survival advantages with few adverse effects compared with the conventional therapy, this immunotherapy as a monotherapy is considered to be insufficient to elicit durable control of cancers and cures.
Nowadays, to improve the efficiency of peptide-based cancer vaccines, combination immunotherapy of peptide-based cancer vaccines together with the immune-checkpoint blockade therapies using mAbs specific for CTLA-4, programmed cell death 1 (PD-1), or PD-1 ligand 1 (PD-L1) have been developed for clinical application. Combination immunotherapy with peptide-based cancer vaccines and immune-checkpoint blockade therapies that are designed concurrently to activate tumor-specific immune responses and inactivate the immunosuppression in the tumor microenvironment may overcome this ineffectiveness, and lead to the induction of stronger anti-tumor responses. Furthermore, the recent technical progress of genetic analysis enables us to evaluate the immunogenicity of tumor cells and the immune status of the tumor microenvironment in individual cancer patients. This information is expected to lead to the discovery of the predictive biomarkers to select patients for treatment with cancer immunotherapy and the development of the personalized peptide-based cancer vaccines that may improve the efficacy of this immunotherapy. In this review, we will outline the current state of cancer vaccine therapy, recent topics, and future prospects, focusing on cancer vaccine therapy using TAAs- and neoantigens-derived peptide and DC.
