Immunotherapy for head and neck cancer

Abstract

Head and neck cancer represents a challenging disease. Despite recent treatment advances, which have improved functional outcomes, the long-term survival of head and neck cancer patients has remained unchanged for the past 25 years. One of the goals of adjuvant cancer therapy is to eradicate local regional microscopic and micrometastatic disease with minimal toxicity to surrounding normal cells. In this respect, antigen-specific immunotherapy is an attractive therapeutic approach. With the advances in molecular genetics and fundamental immunology, antigen-specific immunotherapy is being actively explored using DNA, bacterial vector, viral vector, peptide, protein, dendritic cell, and tumor-cell based vaccines. Early phase clinical trials have demonstrated the safety and feasibility of these novel therapies and the emphasis is now shifting towards the development of strategies, which can increase the potency of these vaccines. As the field of immunotherapy matures and as our understanding of the complex interaction between tumor and host develops, we get closer to realizing the potential of immunotherapy as an adjunctive method to control head and neck cancer and improve long-term survival in this patient population.

Immunotherapy of Head and Neck Cancer: Current and Future Considerations

“…Another advantage is that the immune system can adapt to the evolution of cancer cells and can respond in a systemic fashion [31]. Signs of an immune response have been shown to correlate with positive outcomes for cancer patients.…”

“…One category is tumor-specific antigens (also called germ cell antigens or cancer testes antigens), which are silenced in normal tissues but are reactivated in certain tumors [31]. For example, up to 71% of HNSCCs express antigens from at least 1 of 6 melanoma antigen genes (MAGEs) [57], notably MAGE-1 and MAGE-3 [58].…”

“…Another category of tumor-associated antigen is tumor-specific mutated proteins that are unique to the tumor and may contribute to the malignant phenotype, for example, tumor suppressor gene p53 [31]. Preclinical work suggests not only that p53 is mutated in many more cases of HNSCC than originally thought but also that wild-type p53 is often associated with highly oncogenic strains of HPV (types 16 and 18) [61].…”

“…Notable examples are carcinoembryonic antigen (CEA), HER-2/neu, VEGF, and EGFR [31]. Antigens derived from oncogenic viruses, such as the HPV E6 and E7 oncoproteins, are also important targets in HNSCC [62–64].…”

Innovative DNA vaccine for human papillomavirus (HPV)-associated head and neck cancer

“…The HPV-associated head and neck tumors are derived mainly from the oropharynx, including the tonsil and base of tongue (for review see 3). Thus, immunotherapy targeting HPV antigens has emerged as a promising approach for the treatment of head and neck cancers 4. More than 90% of HPV-associated HNSCC are caused by HPV type 16 5.…”