2021-08-012024-05-17https://scholars.lib.ntu.edu.tw/handle/123456789/689544由於癌症免疫學的演進以及新一代基因定序技術和生物信息學的發展, 個性化癌症疫苗為現今蓬勃發展之領域。相較於單一抗原的傳統癌症疫苗，個性化癌症疫苗源自腫瘤特異性突變並針對患者個體定制，藉而克服癌症異質性和HLA相容性在疫苗製備上帶來的問題。然而, 個人化癌症疫苗仍有許多技術挑戰。舉例來說，在動物研究和早期臨床試驗中，大多數預測的胜肽抗原並未能激活其相應的殺手T細胞,而抗原預測和臨床結果之間的巨大差異預計將成為個人化疫苗臨床轉意的主要障礙，而我們認為疫苗傳遞技術是目前個人化疫苗上最大的技術挑戰。為解決這一問題，本計畫匯集了胡哲銘博士在疫苗奈米技術方面的專業知識，陶秘華博士在癌症免疫學方面專長，科泰名博士在生物信息學方面的技術，以及林淑華博士在擬人化小鼠模型之開發，以優化個性化疫苗的配方設計和驗證。利用本團隊特有的中空奈米顆粒平台有效刺激T細胞並在搭載人類免疫系統的小鼠模型中的進行測試，我們預期可以消除疫苗製備中的不確定性 ，並以直腸癌為主要病症研發出新型的抗癌疫苗。我們也預期通過奈米顆粒疫苗產生的T細胞數據進而更進一步改善新抗原預測演算法。該項目的成功有望為開發，驗證和改進個性化癌症疫苗提供一個高價值的平台。此外，該項目開發的技術有望在奈米醫學和癌症免疫治療領域提供額外的商業價值。 Advances in the understanding of cancer immunology, next-generation sequencing, and bioinformatics have brought forth the tantalizing concept of personalized cancer vaccines. Unlike traditional cancer vaccine concepts based on singular antigen targets, personalized cancer vaccines are derived from tumor-specific mutations and tailored to individual patients, thereby overcoming challenges associated with cancer heterogeneity and HLA compatibility. Despite rising enthusiasm regarding the modular vaccination approach, many technological challenges remain. In particular, in animal studies and early clinical trials, most of the predicted peptide targets failed to induce their corresponding cytotoxic T cell responses. The large discrepancy between computational predictions and clinical results is expected to present a major roadblock in the translation of this promising concept, and we hypothesize that the inadequacy of present vaccine delivery technology is the primary culprit. To address this issue, the present project assembles the expertise of Dr. Che-Ming Jack Hu in vaccine nanotechnology, Dr. Mi-Hua Tao in cancer immunology, Dr. Tai-Ming Ko in bioinformatics, and Dr. Shu-Wha Lin in humanized mouse model development towards improving formulation design and validation of personalized vaccines. By potently stimulating T cell targets with a proprietary hollow nanoparticle platform and rigorously evaluate formulation potency in mouse model with a functioning human immune system, we anticipate to remove the guesswork in vaccine preparation. With colorectal cancer as our primary indication, we expect to develop a safe and potent vaccination approach. Effective multivalent T cell induction by nanoparticle vaccines is also anticipated to generate unambiguous data that may further improve the neoantigen prediction algorithm. Success of this project is expected to offer a compelling platform for developing, validating, and improving personalized cancer vaccines. In addition, technologies developed in this project are anticipated to provide added commercial values in the fields of nanomedicine and cancer immunotherapy.新抗原奈米顆粒疫苗新一代基因定序個性化癌症疫苗擬人化動物模型直腸癌neoantigennanoparticle vaccinenext-generation sequencingpersonalized cancer vaccinehumanize animal modelcolorectal cancer