Therapeutic vaccines for high-risk HPV-associated diseases.

DNA-based vaccination is a promising approach to cancer immunotherapy. DNA-based vaccines specific for tumor-associated antigens (TAAs) are indeed relatively simple to produce, cost-efficient and well tolerated. However, the clinical efficacy of DNA-based vaccines for cancer therapy is considerably limited by central and peripheral tolerance. During the past decade, considerable efforts have been devoted to the development and characterization of novel DNA-based vaccines that would circumvent this obstacle. In this setting, particular attention has been dedicated to the route of administration, expression of modified TAAs, co-expression of immunostimulatory molecules, and co-delivery of immune checkpoint blockers. Here, we review preclinical and clinical progress on DNA-based vaccines for cancer therapy.

https://www.tandfonline.com/doi/pdf/10.1080/2162402X.2017.1398878

Trial watch: DNA-based vaccines for oncological indications.

Head and neck squamous cell carcinoma (HNSCC) is a frequent tumour arising from multiple anatomical subsites in the head and neck region. The treatment for early-stage disease is generally single modality, either surgery or radiotherapy. The treatment for locally advanced tumours is multimodal. For recurrent/metastatic HNSCC palliative chemotherapy is standard of care. The prognosis is limited and novel treatment approaches are urgently needed. HNSCC evades immune responses through multiple resistance mechanisms. HNSCC is particularly characterised by an immunosuppressive environment which includes the release of immunosuppressive factors, activation, expansion of immune cells with inhibitory activity and decreased tumour immunogenicity. An in-depth understanding of these mechanisms led to rational design of immunotherapeutic approaches and clinical trials. Currently, only immune checkpoint inhibitors, namely monoclonal antibodies targeting the immune inhibitory receptor programmed cell death 1 (PD-1) and its ligand PD-L1 have proven clinical efficacy in randomised phase III trials. The PD-1 inhibitor nivolumab is the only drug approved for platinum-refractory recurrent/metastatic HNSCC. However, many more immunotherapeutic treatment options are currently under investigation. Ongoing trials are investigating immunotherapeutic approaches also in the curative setting and combination therapies using different immunotherapeutic approaches. This review article summarises current knowledge of the role of the immune system in the development and progression of HNSCC, and provides a comprehensive overview on the development of immunotherapeutic approaches.

Immunotherapy in head and neck cancer - scientific rationale, current treatment options and future directions.

The immune system plays a key role in preventing tumor formation by recognizing and destroying malignant cells. For over a century, researchers have attempted to harness the immune response as a cancer treatment, although this approach has only recently achieved clinical success. Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide and is associated with cigarette smoking, alcohol consumption, betel nut use, and human papillomavirus infection. Unfortunately, worldwide mortality from HNSCC remains high, partially due to limits on therapy secondary to the significant morbidity associated with current treatments. Therefore, immunotherapeutic approaches to HNSCC treatment are attractive for their potential to reduce morbidity while improving survival. However, the application of immunotherapies to this disease has been challenging because HNSCC is profoundly immunosuppressive, resulting in decreased absolute lymphocyte counts, impaired natural killer cell function, reduced antigen-presenting cell function, and a tumor-permissive cytokine profile. Despite these challenges, numerous clinical trials testing the safety and efficacy of immunotherapeutic approaches to HNSCC treatment are currently underway, many of which have produced promising results. This review will summarize immunotherapeutic approaches to HNSCC that are currently undergoing clinical trials.

https://www.mdpi.com/2072-6694/8/10/87/pdf

Novel immunotherapeutic approaches for head and neck squamous cell carcinoma

Head and neck squamous cell cancer (HNSCC) is a malignancy with a rapidly changing demographic profile, given the recent epidemic of human papilloma virus related cancers Most patients present with locally advanced disease and receive combination therapeutic approaches with curative potential, albeit with significant toxicity Up to a third of patients, however, will eventually develop recurrent or metastatic disease The prognosis of such patients is dismal, as palliative treatment options remain limited Immune-directed therapies offer a novel therapeutic strategy beyond cytotoxic chemotherapy and are currently being evaluated in a wide variety of malignancies HNSCC is a particularly favorable disease for immunotherapy, as immune evasion and dysregulation have been shown to play a key role in the initiation and progression of HNSCC This review focuses on the latest developments in immunotherapy in HNSCC, with a particular focus on checkpoint inhibitors, adoptive cellular therapies, and vaccines

https://journals.sagepub.com/doi/pdf/10.1177/1758834016631529

Immunotherapy for head and neck cancer: latest developments and clinical potential:

Meeting abstracts

Oropharyngeal HNSCCa is frequently associated with HPV infection. DNA-based Immunotherapy with plasmids encoding HPV16 and HPV18 E6/E7 antigens has been shown to generate robust immune responses in women with HPV-driven high-grade cervical dysplasia. We hypothesize that HPV-

https://jitc.bmj.com/content/jitc/3/Suppl_2/P426.full.pdf

Immunotherapy with VGX-3100 (HPV16 and HPV18 plasmids) + INO-9012 (DNA encoding IL-12) in human papillomavirus (HPV) associated head and neck squamous cell carcinoma (HNSCCa): interim safety and immunogenicity results

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Immunotherapy with VGX-3100 (HPV16 and HPV18 plasmids) + INO-9012 (DNA encoding IL-12) in human papillomavirus (HPV) associated head and neck squamous cell carcinoma (HNSCCa): interim safety and immunogenicity results