A phase 1, single centre, open label, escalating dose study to assess the safety, tolerability and immunogenicity of a therapeutic human papillomavirus (HPV) DNA vaccine (AMV002) for HPV-associated head and neck cancer (HNC)

Chandra, Janin; Woo, Wai-Ping; Finlayson, Neil; Liu, Howard; McGrath, Margaret; Ladwa, Rahul; Brauer, Michelle; Xu, Yixin; Hanson, Sarah; Panizza, Benedict; Frazer, Ian H.; Porceddu, Sandro

doi:10.1007/s00262-020-02720-7

Cited by 23 publications

(18 citation statements)

References 35 publications

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“…These cases might be preventable by HPV vaccination (40). Importantly, there has been prospective clinical research to explore the implementation of HPV vaccination in HPV-associated HNSCC (41). Considerable efforts are needed to further propel HPV vaccination program in HNSCC patients.…”

Section: Discussionmentioning

confidence: 99%

HPV Positive Status Is a Favorable Prognostic Factor in Non-Nasopharyngeal Head and Neck Squamous Cell Carcinoma Patients: A Retrospective Study From the Surveillance, Epidemiology, and End Results Database

Wang

Liu

et al. 2021

Front. Oncol.

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ObjectiveTo investigate the impact of the human papillomavirus (HPV) status on head and neck squamous cell carcinoma (HNSCC) arising from different anatomic subsites.MethodsHNSCC patients with known HPV status from the Surveillance, Epidemiology, and End Results (SEER) database between 2010–2015 were included in our analysis. Patients were classified into three categories of HNSCC according to Site recode ICD-O-3/WHO 2008 and Primary Site-labeled, namely, oropharynx, hypopharynx, and nasopharynx. Logistic regression model was conducted to evaluate the relationship between patient characteristics and HPV status. Kaplan-Meier methods and COX regression analysis were used to analyze survival data.ResultsA total of 9,943 HNSCC patients with known HPV status from the SEER database were enrolled, with 6,829 (68.7%) HPV-positive patients. HPV-positive and HPV-negative HNSCC were distinct and had different clinical and socioeconomic features (all P < 0.001). Primary sites, socioeconomical factors (age, sex, marital status, and race), and pathological features (TNM stage and grade) were closely related with HPV status (all P < 0.001). HPV-positive status was a favorable prognostic marker in HNSCC patients with cancers of the oropharynx and hypopharynx (all P < 0.001), but was not in nasopharyngeal carcinoma patients (P = 0.843). A total of 8,933 oropharyngeal carcinoma (OPC) and 558 hypopharyngeal carcinoma (HPC) patients were divided into the training and validation cohorts with a ratio of 1:1. Significant prognostic factors of the OS yielded by multivariate COX analysis in the training cohort were integrated to construct nomograms for OPC and HPC patients. The prognostic models showed a good discrimination with a C-index of 0.79 ± 0.007 and 0.73 ± 0.023 in OPC and HPC, respectively. Favorable calibration was reflected by the calibration curves. Additionally, corresponding risk classification systems for OPC and HPC patients based on the nomograms were built and could perfectly classify patients into low-risk, intermediated-risk, high-risk groups. OS in the three risk groups was accurately differentiated and showed a good discrimination.ConclusionHPV positivity was associated with an improved survival in HNSCC patients with cancers of the oropharynx and hypopharynx. Nomograms and corresponding risk classification systems were constructed to assist clinicians in evaluating the survival of OPC and HPC patients.

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Section: Discussionmentioning

confidence: 99%

HPV Positive Status Is a Favorable Prognostic Factor in Non-Nasopharyngeal Head and Neck Squamous Cell Carcinoma Patients: A Retrospective Study From the Surveillance, Epidemiology, and End Results Database

Wang

Liu

et al. 2021

Front. Oncol.

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“…They are cost-efficient, stable, and safe in handling ( Figure 2 ). The effectiveness of a DNA vaccine containing two plasmids encoding a fusion protein of the HPV-16 E6 and E7 viral sequences was tested in a phase I clinical trial in HPV-associated oropharyngeal squamous cell carcinoma patients, previously treated by radiotherapy [ 77 ]. An enhancing of the specific immunity to virus-derived TAAs in patients was observed.…”

Section: Cd4 T Cells In Cancer Vaccinationmentioning

confidence: 99%

Impact of Immunotherapy on CD4 T Cell Phenotypes and Function in Cancer

et al. 2021

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Immunotherapy has become a standard treatment in many cancers and it is based on three main therapeutic axes: immune checkpoint blockade (ICB), vaccination and adoptive cell transfer (ACT). If originally these therapies mainly focused on exploiting CD8 T cells given their role in the direct elimination of tumor cells, increasing evidence highlights the crucial role CD4 T cells play in the antitumor immune response. Indeed, these cells can profoundly modulate the tumor microenvironment (TME) by secreting different types of cytokine or by directly eliminating cancer cells. In this review, we describe how different CD4 T cell subsets can contribute to tumor immune responses during immunotherapy and the novel high-throughput immune monitoring tools that are expected to facilitate the study of CD4 T cells, at antigen-specific and single cell level, thus accelerating bench-to-bed translational research in cancer.

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“…Multiple combinations and formulations expressing HPV E2 protein or E6 and E7 oncogenes, ranging from peptide vaccines to DNA modified plasmids, have been tested in pre-cancerous HPV + intraepithelial neoplasia, cervical cancer and HPV + H&N SCCs, where they have demonstrated good tolerability and the induction of vaccinespecific T-cell responses. However, some of the tested vaccines did not offered survival benefits and others are still in the process of being clinically evaluated as monotherapy or in combination with ICIs [49,54]. Some of these therapeutic vaccines prevent the reappearance of lesions in the mild forms of the HPV-derived disease [50].…”

Section: Discussionmentioning

confidence: 99%

“…Our laboratory has recently finished a Phase I dose escalation clinical trials of the AMV002 vaccine, a DNA vaccine consisting of a mixture of NTC8485-O-UE6E7 and NTC8485-O-s-E6E7 plasmids that express a codon optimized recombinant HPV16 E6E7 fusion protein with a single ubiquitin sequence repeat (-O-UE6E7) or a murine IgK secretory sequence (O-s-E6E7). This DNA vaccine was trialled in conventionally treated HPV16 + Oropharyngeal Squamous cell carcinoma patients (OPSCC) with no evidence of recurrent and/or metastatic disease [54]. AMV002 was well tolerated and elevated specific T-cell immune responses to E6-and/or E7 antigens in 10 of the 12 treated patients (83.3%) with an observed four-fold increase in E6/E7 antibody titers in one out of four patients in the highest dose cohort (4 mg).…”

Section: Hpvmentioning

confidence: 99%

Evolution of Cancer Vaccines—Challenges, Achievements, and Future Directions

et al. 2021

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The development of cancer vaccines has been intensively pursued over the past 50 years with modest success. However, recent advancements in the fields of genetics, molecular biology, biochemistry, and immunology have renewed interest in these immunotherapies and allowed the development of promising cancer vaccine candidates. Numerous clinical trials testing the response evoked by tumour antigens, differing in origin and nature, have shed light on the desirable target characteristics capable of inducing strong tumour-specific non-toxic responses with increased potential to bring clinical benefit to patients. Novel delivery methods, ranging from a patient’s autologous dendritic cells to liposome nanoparticles, have exponentially increased the abundance and exposure of the antigenic payloads. Furthermore, growing knowledge of the mechanisms by which tumours evade the immune response has led to new approaches to reverse these roadblocks and to re-invigorate previously suppressed anti-tumour surveillance. The use of new drugs in combination with antigen-based therapies is highly targeted and may represent the future of cancer vaccines. In this review, we address the main antigens and delivery methods used to develop cancer vaccines, their clinical outcomes, and the new directions that the vaccine immunotherapy field is taking.

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A phase 1, single centre, open label, escalating dose study to assess the safety, tolerability and immunogenicity of a therapeutic human papillomavirus (HPV) DNA vaccine (AMV002) for HPV-associated head and neck cancer (HNC)

Cited by 23 publications

References 35 publications

HPV Positive Status Is a Favorable Prognostic Factor in Non-Nasopharyngeal Head and Neck Squamous Cell Carcinoma Patients: A Retrospective Study From the Surveillance, Epidemiology, and End Results Database

HPV Positive Status Is a Favorable Prognostic Factor in Non-Nasopharyngeal Head and Neck Squamous Cell Carcinoma Patients: A Retrospective Study From the Surveillance, Epidemiology, and End Results Database

Impact of Immunotherapy on CD4 T Cell Phenotypes and Function in Cancer

Evolution of Cancer Vaccines—Challenges, Achievements, and Future Directions

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