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在有袋动物袋獾中表达的热休克蛋白是针对袋獾面部肿瘤病疫苗的潜在抗原候选物。

Heat shock proteins expressed in the marsupial Tasmanian devil are potential antigenic candidates in a vaccine against devil facial tumour disease.

机构信息

Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.

Central Science Laboratory, University of Tasmania, Hobart, Tasmania, Australia.

出版信息

PLoS One. 2018 Apr 27;13(4):e0196469. doi: 10.1371/journal.pone.0196469. eCollection 2018.

Abstract

The Tasmanian devil (Sarcophilus harrisii), the largest extant carnivorous marsupial and endemic to Tasmania, is at the verge of extinction due to the emergence of a transmissible cancer known as devil facial tumour disease (DFTD). DFTD has spread over the distribution range of the species and has been responsible for a severe decline in the global devil population. To protect the Tasmanian devil from extinction in the wild, our group has focused on the development of a prophylactic vaccine. Although this work has shown that vaccine preparations using whole DFTD tumour cells supplemented with adjuvants can induce anti-DFTD immune responses, alternative strategies that induce stronger and more specific immune responses are required. In humans, heat shock proteins (HSPs) derived from tumour cells have been used instead of whole-tumour cell preparations as a source of antigens for cancer immunotherapy. As HSPs have not been studied in the Tasmanian devil, this study presents the first characterisation of HSPs in this marsupial and evaluates the suitability of these proteins as antigenic components for the enhancement of a DFTD vaccine. We show that tissues and cancer cells from the Tasmanian devil express constitutive and inducible HSP. Additionally, this study suggests that HSP derived from DFTD cancer cells are immunogenic supporting the future development of a HSP-based vaccine against DFTD.

摘要

袋獾(Sarcophilus harrisii)是现存最大的肉食有袋动物,仅分布于塔斯马尼亚岛,由于一种名为袋獾面部肿瘤病(DFTD)的传染性癌症的出现,它们正处于灭绝的边缘。DFTD 已经在该物种的分布范围内传播,并导致全球袋獾数量严重下降。为了保护袋獾在野外灭绝,我们的团队专注于开发一种预防性疫苗。尽管这项工作表明,使用添加佐剂的整个 DFTD 肿瘤细胞制备的疫苗可以诱导抗 DFTD 免疫反应,但需要诱导更强和更特异的免疫反应的替代策略。在人类中,源自肿瘤细胞的热休克蛋白(HSPs)已被用作癌症免疫疗法的抗原来源,而不是使用整个肿瘤细胞制剂。由于 HSPs 在袋獾中尚未被研究,本研究首次对这种有袋动物的 HSPs 进行了表征,并评估了这些蛋白作为增强 DFTD 疫苗的抗原成分的适用性。我们表明,袋獾的组织和癌细胞表达组成型和诱导型 HSP。此外,这项研究表明,源自 DFTD 癌细胞的 HSP 具有免疫原性,支持未来开发针对 DFTD 的 HSP 疫苗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51e6/5922574/288b5add4ec5/pone.0196469.g001.jpg

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