Head & Neck Cancer Neoantigen Characterization & Therapeutic Targeting

头

• 批准号: 10436179
• 负责人: SEBASTIAN JOYCE
• 金额: $ 44.76万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10436179
• 关键词: Adjuvant; Algorithms; Antigens; Antitumor Response; Autologous; Bioinformatics; Cancer Patient; Cancer Vaccines; Cells; Chronic; Clinical; Clinical Trials; Data; Development; Epitope spreading; Epitopes; Formulation; Future; Goals; HLA-A2 Antigen; Head Cancer; Head and Neck Squamous Cell Carcinoma; Head and neck structure; Human; Human Papillomavirus; Immune checkpoint inhibitor; Immunologics; Immunotherapeutic agent; Interferons; Longitudinal cohort; MHC Class I Genes; Malignant neoplasm of larynx; Maps; Mass Spectrum Analysis; Metastatic/Recurrent; Methods; Mission; Modality; Modeling; Mus; Mutation; National Institute of Dental and Craniofacial Research; Neck Cancer; Neoadjuvant Therapy; Nivolumab; Operative Surgical Procedures; Oral health; Patients; Peptides; Proteomics; STING agonists; Specimen; System; T cell response; T-Lymphocyte; Testing; Therapeutic Agents; United States National Institutes of Health; Vaccines; base; cancer immunotherapy; cancer therapy; cancer type; checkpoint therapy; clinical translation; combinatorial; delivery vehicle; exome sequencing; experimental study; head and neck cancer patient; humanized mouse; improved; in silico; in vivo; in vivo Model; malignant mouth neoplasm; malignant oropharynx neoplasm; mouse model; multiple reaction monitoring; nanoparticle; nanoparticle delivery; neoantigens; neoplastic cell; novel; novel strategies; patient derived xenograft model; personalized immunotherapy; pre-clinical; prediction algorithm; response; response biomarker; single cell sequencing; targeted treatment; therapeutic target; tobacco exposure; transcriptome sequencing; translational impact; tumor; tumor immunology; whole genome

Project Summary Head & neck squamous cell carcinoma (HNSCC) is currently showing clinical response to immune checkpoint inhibitors, but its efficacy is still low at nearly 20% of the recurrent/metastatic patients treated. One immunological strategy to improve upon this low efficacy rate is to target the high mutational burden of HNSCC, particularly those associated with chronic tobacco exposure. We propose to characterize the mutation associated neoantigen landscape of human HNSCC obtained from patients treated with nivolumab in a neoadjuvant setting using both in silico and mass spectroscopy methods to directly obtain these human neo- epitopes. In conjunction with these studies, we will characterize the immunodominant MHC restricted neoantigens in an autologous humanized murine system in vivo. These findings will help direct a novel strategy to expand these neoantigen-specific T-cells using a potent STING agonist formulated nanoparticles with known neoantigens found in human HNSCC. Findings from this proposal will also impact how neoantigen-based cancer vaccines should be administered in conjunction with immune checkpoint inhibitors in future head and neck clinical trials. Lastly, our proposal will also inform neoepitope prediction algorithms and antigen based trials for other cancer types to have deep impact in the field of cancer immunology as a whole.

项目总结

项目成果

Discordant Responses Between Primary Head and Neck Tumors and Nodal Metastases Treated With Neoadjuvant Nivolumab: Correlation of Radiographic and Pathologic Treatment Effect.

用新辅助纳武利尤单抗治疗的原发性头颈肿瘤与淋巴结转移之间的不一致反应：放射学和病理治疗效果的相关性。

• DOI: 10.3389/fonc.2020.566315
• 发表时间: 2020
• 期刊: Frontiers in oncology
• 影响因子: 4.7
• 作者: Merlino DJ;Johnson JM;Tuluc M;Gargano S;Stapp R;Harshyne L Jr;Leiby BE;Flanders A;Zinner R;Axelrod R;Curry J;Cognetti DM;Mannion K;Kim YJ;Rodeck U;Argiris A;Luginbuhl AJ
• 通讯作者: Luginbuhl AJ

Efferocytosis drives myeloid NLRP3 dependent inflammasome signaling secretion of IL-1β to promote tumor growth.

• DOI: 10.3389/fimmu.2022.993771
• 发表时间: 2022
• 期刊: FRONTIERS IN IMMUNOLOGY
• 影响因子: 7.3
• 作者: Lang, Cara;Roy, Sohini;Wang, Yu;Graves, Diana;Xu, Yaomin;Serezani, C. Henrique;Korrer, Michael;Kim, Young J.
• 通讯作者: Kim, Young J.

Know thy immune self and non-self: Proteomics informs on the expanse of self and non-self, and how and where they arise.

• DOI: 10.1002/pmic.202000143
• 发表时间: 2021-12
• 期刊: Proteomics
• 影响因子: 3.4
• 作者: Joyce S;Ternette N
• 通讯作者: Ternette N

Immunotherapy: Who Is Eligible?

免疫疗法：谁有资格？

• DOI: 10.1016/j.otc.2017.04.006
• 发表时间: 2017
• 期刊: Otolaryngologic clinics of North America
• 影响因子: 1.7
• 作者: Wang,Daniel;Gilbert,Jill;Kim,YoungJ
• 通讯作者: Kim,YoungJ

Combined assessment of MHC binding and antigen abundance improves T cell epitope predictions.

• DOI: 10.1016/j.isci.2022.103850
• 发表时间: 2022-02-18
• 期刊: iScience
• 影响因子: 5.8
• 作者: Koşaloğlu-Yalçın Z;Lee J;Greenbaum J;Schoenberger SP;Miller A;Kim YJ;Sette A;Nielsen M;Peters B
• 通讯作者: Peters B