首個癌癥疫苗已通過FDA批準上市,。據(jù)The Journal of the National Cancer Institute
刊登的一則研究表明目前,,一些針對一系列腫瘤相關(guān)抗原的癌癥治療疫苗正在進行臨床試驗評估,。
腫瘤微環(huán)境和其他免疫抑制實體可能限制了癌癥疫苗的有效性,。為了克服避免這一現(xiàn)象,,無論是疫苗與免疫關(guān)鍵節(jié)點(checkpoint)抑制劑,、某些化療藥物和小分子靶向制劑,、輻射療法都要經(jīng)過臨床前和臨床研究評估。
國家癌癥研究所癌癥研究中心的腫瘤免疫學和生物學實驗室Jeffrey Schlom博士詳細概述了目前正處于臨床前研發(fā)階段,、隨機臨床II期和III臨床試驗階段的不同疫苗,。一些疫苗開始在那些已經(jīng)接受過多種治療手段的轉(zhuǎn)移性癌癥患者身上進行初步評估。但臨床研究顯示只有那些只接受過用較少的化療方案治療,,并且距下次化療有很長時間(兩次化療之間時間差很長)的癌癥病人,,對疫苗會更有反應。
作者補充道:疫苗療法最讓人驚奇的地方就是它能作用于與癌癥“干細胞”或上皮間質(zhì)轉(zhuǎn)化(EMT)過程有密切聯(lián)系的分子,,而癌癥“干細胞”或上皮間質(zhì)轉(zhuǎn)化(EMT)過程都是與腫瘤耐藥有關(guān),。
作者寫道:未來癌癥疫苗將會與一系列介入治療聯(lián)用,當前和未來的臨床試驗設(shè)計將由接受輔助治療或新輔助治療的慢性轉(zhuǎn)移性的腫瘤患者組成,。當治療性疫苗的長期安全性確認后,,它們最有可能用于高風險的癌癥患者如會發(fā)展成前列腺癌的高級別前列腺上皮內(nèi)瘤病變患者、發(fā)展大腸癌的家族性腺瘤性息肉患者,。Schlom寫道:“許多研究都表明在化療前分析大腸癌和其它類型癌癥組織切片中免疫浸潤情況,,可以作為一個強有力的生存獨立預后指標。”
他補充說:了解癌細胞的EMT表型和基因突變情況,,我們就能找出研發(fā)癌癥疫苗的新靶標,。(生物谷 Bioon.com)
doi:10.1093/jnci/djs033
PMC:
PMID:
Therapeutic Cancer Vaccines: Current Status and Moving Forward
Jeffrey Schlom
Concurrent with US Food and Drug Administration (FDA) approval of the first therapeutic cancer vaccine, a wide spectrum of other cancer vaccine platforms that target a diverse range of tumor-associated antigens is currently being evaluated in randomized phase II and phase III trials. The profound influence of the tumor microenvironment and other immunosuppressive entities, however, can limit the effectiveness of these vaccines. Numerous strategies are currently being evaluated both preclinically and clinically to counteract these immunosuppressive entities, including the combined use of vaccines with immune checkpoint inhibitors, certain chemotherapeutics, small-molecule targeted therapies, and radiation. The potential influence of the appropriate patient population and clinical trial endpoint in vaccine therapy studies is discussed, as well as the potential importance of biomarkers in future directions of this field.