Intra-cheek immunization as a novel vaccination route for therapeutic vaccines of head and neck squamous cell carcinomas using plasmo virus-like particles
Intra-cheek immunization as a novel vaccination route for therapeutic vaccines of head and neck squamous cell carcinomas using plasmo virus-like particles
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DOI：
10.1080/2162402x.2016.1164363
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发表时间：
2016-01-01
期刊：
影响因子：
7.2
通讯作者：
Lemoine, Francois M.
中科院分区：
文献类型：
--
作者：
Macedo, Rodney;Rochefort, Juliette;Lemoine, Francois M.
尽管目前的治疗方法，头颈部鳞状细胞癌（HNSCCs）起源于上气道消化道的不同粘膜部位，经常以局部-区域的方式复发，预后较差。我们的目的是在临床前原位HNSCCs模型中验证一种使用等离子体病毒样颗粒（pVLPs）接种的创新粘膜途径。为此，我们使用pVLP-E7（一种编码逆转录病毒样颗粒的质粒DNA，携带来自HPV-16的截断的E7癌蛋白作为抗原模型）接种植入口腔黏膜的携带预先建立的TC-1肿瘤的小鼠。pVLP-E7联合临床级TLR激动剂（咪喹莫特和CpG-ODN）。在这个肿瘤微环境类似于人类HNSCCs的临床前原位模型中，研究人员测试了不同的粘膜接种途径是否能引发有效的免疫和抗肿瘤反应。结果表明，与皮内接种（ID）相比，使用pVLP-E7接种粘膜颊内（IC）疫苗可在肿瘤引流淋巴结（tdln）和肿瘤微环境中动员更高的粘膜（CD49a(+)） CD8（+）特异性效应T细胞，从而产生更好的抗肿瘤效果，并对肿瘤再攻击具有长期保护作用。体内CD8（+）缺失表明，抗肿瘤作用完全依赖于CD8(+) T细胞的存在。使用临床前原位HNSCC模型验证pVLPs联合佐剂的IC粘膜疫苗接种，为快速设想在HNSCC患者中使用这种治疗性疫苗提供了有价值的临床前数据，因为疫苗成分和佐剂可以很容易地作为临床级试剂获得。
Despite current therapy, head and neck squamous cell carcinomas (HNSCCs) arising from various mucosal sites of the upper aero-digestive tract frequently relapse in a loco-regional manner and have a poor prognosis. Our objective was to validate an innovative mucosal route of vaccination using plasmo virus-like particles (pVLPs) in a pre-clinical orthotopic model of HNSCCs. For this purpose, we used pVLP-E7, that are plasmid DNA encoding retroviral virus-like particles carrying a truncated E7 oncoprotein from HPV-16 as antigen model, to vaccinate mice bearing pre-established TC-1 tumors implanted into the buccal mucosa. pVLP-E7 were combined with clinical grade TLR agonists (Imiquimod and CpG-ODN). In this pre-clinical orthotopic model, whose tumor microenvironment resembles to those of human HNSCCs, different mucosal vaccination routes were tested for their ability to elicit efficient immune and antitumoral responses. Results showed that mucosal intra-cheek (IC) vaccinations using pVLP-E7, comparatively to intradermic vaccinations (ID), gave rise to higher mobilization of mucosal (CD49a(+)) CD8(+) specific effector T cells in both tumor draining lymph nodes (TdLNs) and tumor microenvironment resulting in better antitumor effects and in a long-term protection against tumor rechallenge. In vivo CD8(+) depletion demonstrated that antitumoral effects were fully dependent upon the presence of CD8(+) T cells. Validation of IC mucosal vaccinations with pVLPs combined with adjuvants using a pre-clinical orthotopic model of HNSCC provides valuable pre-clinical data to rapidly envision the use of such therapeutic vaccines in patients with HNSCCs, inasmuch as vaccinal components and adjuvants can be easily obtained as clinical grade reagents.