Cancer immunotherapy using novel tumor-associated antigenic peptides identified by genome-wide cDNA microarray analyses.
Cancer immunotherapy using novel tumor-associated antigenic peptides identified by genome-wide cDNA microarray analyses.
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DOI：
10.1111/cas.12650
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发表时间：
2015-05
期刊：
影响因子：
5.7
通讯作者：
Shinohara M
中科院分区：
文献类型：
--
作者：
Nishimura Y;Tomita Y;Yuno A;Yoshitake Y;Shinohara M
最近对综合肿瘤类型基因表达谱的全基因组cDNA微阵列分析，结合激光微束显微解剖分离癌症组织，揭示了理想的肿瘤相关抗原（TAAs），这些抗原在包括头颈部鳞状细胞癌（HNSCC）和肺癌在内的各种癌症中经常过表达，但在除睾丸、胎盘和胎儿器官外的大多数正常组织中并不表达。利用hla转基因小鼠和体外人T细胞进行的临床前研究表明，taa来源的ctl表位短肽（SPs）具有高度免疫原性，可诱导HLA-A2或- a24限制性ctl。基于积累的证据，我们在37例晚期HNSCC患者中开展了TAA-SP疫苗的II期临床试验。该研究显示，taa特异性ctl在大多数患者中具有显著的诱导作用，且无严重的不良反应。重要的是，在本研究中观察到包括完全缓解在内的临床反应。另一项治疗性TAA-SP疫苗的II期临床试验正在接受治疗性手术的HNSCC患者中进行，旨在评估预防复发的能力。在人类临床前研究和HLA I类转基因小鼠体内研究的进一步研究表明，taa衍生的长肽（TAA-LPs）不仅能够通过交叉呈递机制诱导混杂的HLA ii类限制性CD4+ T辅助型1细胞，还能够诱导肿瘤特异性ctl。此外，我们观察到接种TAA-SPs的HNSCC患者taa - lp特异性T辅助1型细胞反应和肿瘤抗原扩散增强。这些积累的证据表明，治疗性TAA-SPs和LPs疫苗可能是一种很有前途的癌症免疫治疗方法。
Recent genome-wide cDNA microarray analysis of gene expression profiles in comprehensive tumor types coupled with isolation of cancer tissues by laser-microbeam microdissection have revealed ideal tumor-associated antigens (TAAs) that are frequently overexpressed in various cancers including head and neck squamous cell cancer (HNSCC) and lung cancer, but not in most normal tissues except for testis, placenta, and fetal organs. Preclinical studies using HLA-transgenic mice and human T cells in vitro showed that TAA-derived CTL-epitope short peptides (SPs) are highly immunogenic and induce HLA-A2 or -A24-restricted CTLs. Based on the accumulated evidence, we carried out a phase II clinical trial of the TAA-SP vaccine in advanced 37 HNSCC patients. This study showed a significant induction of TAA-specific CTLs in the majority of patients without serious adverse effects. Importantly, clinical responses including a complete response were observed in this study. Another phase II clinical trial of therapeutic TAA-SP vaccine, designed to evaluate the ability of prevention of recurrence, is ongoing in HNSCC patients who have received curative operations. Further studies in human preclinical studies and in vivo studies using HLA class I transgenic mice showed TAA-derived long peptides (TAA-LPs) have the capacity to induce not only promiscuous HLA class II-restricted CD4+ T helper type 1 cells but also tumor-specific CTLs through a cross-presentation mechanism. Moreover, we observed an augmentation of TAA-LP-specific T helper type 1 cell responses and tumor antigen-spreading in HNSCC patients vaccinated with TAA-SPs. This accumulated evidence suggests that therapeutic TAA-SPs and LPs vaccines may provide a promising cancer immunotherapy.
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影响因子：
11.2
作者：
Corbiere, Veronique;Chapiro, Jacques;Coulie, Pierre G.
通讯作者：
Coulie, Pierre G.
影响因子：
6.4
作者：
Harao, Michiko;Hirata, Shinya;Nishimura, Yasuharu
通讯作者：
Nishimura, Yasuharu
影响因子：
82.9
作者：
通讯作者：
--
DOI：
10.1056/nejmoa1200694
发表时间：
2012-06-28
期刊：
The New England journal of medicine
影响因子：
--
作者：
Brahmer JR;Tykodi SS;Chow LQ;Hwu WJ;Topalian SL;Hwu P;Drake CG;Camacho LH;Kauh J;Odunsi K;Pitot HC;Hamid O;Bhatia S;Martins R;Eaton K;Chen S;Salay TM;Alaparthy S;Grosso JF;Korman AJ;Parker SM;Agrawal S;Goldberg SM;Pardoll DM;Gupta A;Wigginton JM
通讯作者：
Wigginton JM
影响因子：
5.4
作者：
Jung, Keun-Ok;Khan, Asif M.;August, J. Thomas
通讯作者：
August, J. Thomas