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端粒酶和 HER-2/neu 作为犬基因癌症疫苗的靶点。

Telomerase and HER-2/neu as targets of genetic cancer vaccines in dogs.

机构信息

Oncology Department, IRBM - Istituto di Ricerche di Biologia Molecolare, Via Pontina Km 30.600, 00040 Pomezia, Rome, Italy.

出版信息

Vaccine. 2010 Feb 3;28(5):1201-8. doi: 10.1016/j.vaccine.2009.11.031. Epub 2009 Nov 26.

Abstract

Pet dogs represent a valuable pre-clinical model to assess the efficacy of oncology drugs. Additionally, canine cancers occur with an incidence similar to that of humans and share many features with human malignancies including histological appearance, tumor genetics, biological behavior and response to conventional therapies. The telomerase reverse transcriptase (TERT) is reactivated in most of human and dog tumors. Similarly, HER-2/neu oncoprotein is overexpressed in a proportion of canine breast cancers. Therefore, TERT and HER-2/neu can constitute valid tumor associated antigens (TAA), suitable targets for translational cancer immunotherapy in dogs. In this study, we have evaluated the ability of DNA electroporation (DNA-EP) and Adenovirus serotype 6 (Ad6) to induce immune responses against dog TERT (dTERT) and HER-2/neu in healthy dogs. Vaccination was effective in all treated animals and the adaptive immune response remained detectable and long-lasting in the absence of autoimmunity or other side-effects. Our results show that DNA-EP/Ad6-based cancer vaccine induces adaptive immune responses against TAA in canine subjects and support further evaluation of this approach in cancer dog patients.

摘要

宠物犬是评估肿瘤药物疗效的有价值的临床前模型。此外,犬类癌症的发病率与人类相似,并且与人类恶性肿瘤具有许多共同特征,包括组织学外观、肿瘤遗传学、生物学行为和对常规治疗的反应。端粒酶逆转录酶(TERT)在大多数人类和犬类肿瘤中被重新激活。同样,HER-2/neu 癌蛋白在一部分犬乳腺癌中过表达。因此,TERT 和 HER-2/neu 可以构成有效的肿瘤相关抗原(TAA),适合用于犬的转化癌症免疫治疗。在这项研究中,我们评估了 DNA 电穿孔(DNA-EP)和腺病毒血清型 6(Ad6)在健康犬中诱导针对犬 TERT(dTERT)和 HER-2/neu 的免疫反应的能力。在所有接受治疗的动物中,疫苗接种均有效,并且在没有自身免疫或其他副作用的情况下,适应性免疫反应仍然可检测且持久。我们的结果表明,基于 DNA-EP/Ad6 的癌症疫苗可在犬类受试者中诱导针对 TAA 的适应性免疫反应,并支持进一步评估该方法在癌症犬患者中的应用。

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