Targeting Head and Neck Cancer by Vaccination (original) (raw)
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Therapeutic Vaccination in Head and Neck Squamous Cell Carcinoma—A Review
Vaccines
Therapeutic vaccination is one of the most effective immunotherapeutic approaches, second only to immune checkpoint inhibitors (ICIs), which have already been approved for clinical use. Head and neck squamous cell carcinomas (HNSCCs) are heterogenous epithelial tumors of the upper aerodigestive tract, and a significant proportion of these tumors tend to exhibit unfavorable therapeutic responses to the existing treatment options. Comprehending the immunopathology of these tumors and choosing an appropriate immunotherapeutic maneuver seems to be a promising avenue for solving this problem. The current review provides a detailed overview of the strategies, targets, and candidates for therapeutic vaccination in HNSCC. The classical principle of inducing a potent, antigen-specific, cell-mediated cytotoxicity targeting a specific tumor antigen seems to be the most effective mechanism of therapeutic vaccination, particularly against the human papilloma virus positive subset of HNSCC. Howev...
MDPI Viruses, 2015
The rise in human papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HNSCC) has elicited significant interest in the role of high-risk HPV in tumorigenesis. Because patients with HPV-positive HNSCC have better prognoses than do their HPV-negative counterparts, current therapeutic strategies for HPV + HNSCC are increasingly considered to be overly aggressive, highlighting a need for customized treatment guidelines for this cohort. Additional issues include the unmet need for a reliable screening strategy for HNSCC, as well as the ongoing assessment of the efficacy of prophylactic vaccines for the prevention of HPV infections in the head and neck regions. This review also outlines a number of emerging prospects for therapeutic vaccines, as well as for targeted, molecular-based therapies for HPV-associated head and neck cancers. Overall, the future for developing novel and effective therapeutic agents for HPV-associated head and neck tumors is promising; continued progress is critical in order to meet the challenges posed by the growing epidemic.
Cancer Immunology, Immunotherapy, 2020
Background We conducted a phase 1 dose escalation study (ACTRN12618000140257 registered on 30/01/2018) to evaluate the safety, tolerability and immunogenicity of a therapeutic human papillomavirus (HPV) DNA vaccine (AMV002) in subjects previously treated for HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). Methods Eligible subjects had to have no evidence of recurrent and/or metastatic disease at least 12 weeks following the completion of treatment. Three dosing cohorts each consisted of four subjects: group 1: 0.25 mg/dose, group 2: 1 mg/dose, group 3: 4 mg/dose. AMV002 was delivered intradermally on days 0, 28 and 56. Incidence and severity of treatment-emergent adverse events (TEAE) including local reaction at the injection site, and vaccination compliance were recorded. T cell and antibody responses to HPV16 E6 and E7 were measured by interferon gamma (IFN-γ) enzyme-linked immunosorbent spot (ELISpot) assay and enzyme-linked immunosorbent assay (ELISA). Results All subjects completed the vaccination programme and experienced mild discomfort at the injection site(s). Preimmunisation, cell-mediated responses to HPV16 E6 and E7 were evident in all subjects, and E7-specific antibodies were detected in 11 (91.7%), reflecting previous exposure to HPV. Post-vaccination, 10 of 12 (83.3%) subjects responded to one or more of the E6 and/or E7 peptide pools, while 2 (16.7%) did not show additional vaccine-induced cell-mediated responses. Vaccination resulted in a ≥ 4-fold increase in anti-HPV16 E7 antibody titre in one subject in group 3. Conclusions AMV002 was well tolerated at all dose levels and resulted in enhanced specific immunity to virus-derived tumour-associated antigens in subjects previously treated for HPV-associated OPSCC. Keywords Human papillomavirus • Head and neck cancer • Oropharyngeal squamous cell carcinoma • Immunotherapy • DNA vaccine • HPV E6 and E7 oncoproteins Abbreviations ELISA Enzyme-linked immunosorbent assay ELISpot Enzyme-linked immunosorbent spot HPV Human papillomavirus HNC Head and neck cancer IFNγ Interferon gamma OPSCC Oropharyngeal squamous cell carcinoma PBMC Peripheral blood mononuclear cells TEAE Treatment emergent adverse events J. Chandra and W. P. Woo contributed equally.
2015
Abstract: The rise in human papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HNSCC) has elicited significant interest in the role of high-risk HPV in tumorigenesis. Because patients with HPV-positive HNSCC have better prognoses than do their HPV-negative counterparts, current therapeutic strategies for HPV+ HNSCC are increasingly considered to be overly aggressive, highlighting a need for customized treatment guidelines for this cohort. Additional issues include the unmet need for a reliable screening strategy for HNSCC, as well as the ongoing assessment of the efficacy of prophylactic vaccines for the prevention of HPV infections in the head and neck regions. This review also outlines a number of emerging prospects for therapeutic vaccines, as well as for targeted, molecular-based therapies for HPV-associated head and neck cancers. Overall, the future for developing novel and effective therapeutic agents for HPV-associated head and neck tumors is promising; co...
Immunotherapy for head and neck cancer
Anti-Cancer Drugs, 2011
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 for head and neck cancer patients: shifting the balance
Immunotherapy, 2013
Head and neck squamous cell carcinoma is the sixth most common cancer in the western world. Over the last few decades little improvement has been made to increase the relatively low 5-year survival rate. This calls for novel and improved therapies. Here, we describe opportunities in immunotherapy for head and neck cancer patients and hurdles yet to be overcome. Viruses are involved in a subset of head and neck squamous cell carcinoma cases. The incidence of HPV-related head and neck cancer is increasing and is a distinctly different disease from other head and neck carcinomas. Virus-induced tumors express viral antigens that are good targets for immunotherapeutic treatment options. The type of immunotherapeutic treatment, either active or passive, should be selected depending on the HPV status of the tumor and the immune status of the patient.
Frontiers in Immunology, 2021
HPV-independent head and neck squamous cell carcinoma (HNSCC) is a common cancer globally. The overall response rate to anti-PD1 checkpoint inhibitors (CPIs) in HNSCC is ~16%. One major factor influencing the effectiveness of CPI is the level of tumor infiltrating T cells (TILs). Converting TILlow tumors to TILhigh tumors is thus critical to improve clinical outcome. Here we describe a novel DNA vaccines to facilitate the T-cell infiltration and control tumor growth. We evaluated the expression of target antigens and their respective immunogenicity in HNSCC patients. The efficacy of DNA vaccines targeting two novel antigens were evaluated with or without CPI using a syngeneic model. Most HNSCC patients (43/44) co-expressed MAGED4B and FJX1 and their respective tetramer-specific T cells were in the range of 0.06-0.12%. In a preclinical model, antigen-specific T cells were induced by DNA vaccines and increased T cell infiltration into the tumor, but not MDSC or regulatory T cells. The...
Human vaccines & immunotherapeutics, 2015
The incidence of oropharyngeal squamous cell carcinoma (OPSCC) related to human papillomavirus (HPV) is increasing at a dramatic rate, with men affected more commonly than women. Individuals who develop this disease suffer significant morbidity and potential mortality from their cancer and its associated treatment. We aim to evaluate the possible impact that the currently available HPV vaccines will have on this group of cancers. Available peer-reviewed literature, practice guidelines, and statistics published by the Center for Disease Control and Prevention. Contemporary peer-reviewed medical literature was selected based on its scientific validity and relevance to the impact HPV vaccination may have on the morbidity, mortality and cost resulting from HPV-related OPSCC in the United States. The incidence of HPV-related OPSCC is increasing at a near epidemic rate in the United States. The cost of treatment of HPV-related OPSCC is high, and the disease and its therapy result in signi...