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

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.

塔斯马尼亚魔鬼（Sarcophilus harrisii），作为现存最大的有袋类肉食性动物，且仅产于塔斯马尼亚岛，正面临着灭绝的危机，这一危机的导火索是一种名为塔斯马尼亚魔鬼面部肿瘤病（DFTD）的传染性癌症。DFTD已蔓延至该物种的分布范围，并导致了全球塔斯马尼亚魔鬼数量的急剧下降。为了保护塔斯马尼亚魔鬼在野外的生存，我们团队致力于开发一种预防性疫苗。尽管使用整个DFTD肿瘤细胞并辅以佐剂制备的疫苗已显示出能够诱导抗DFTD的免疫反应，但仍需探索能够诱导更强、更特异性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）已被用作抗原来源，用于癌症免疫疗法，而不再使用整个肿瘤细胞制备。由于HSPs在塔斯马尼亚魔鬼中尚未得到研究，本研究首次对这种有袋动物的HSP进行了表征，并评估了这些蛋白质作为抗原成分用于增强DFTD疫苗的适宜性。我们发现，塔斯马尼亚魔鬼的组织和癌细胞表达构成性和可诱导性HSP。此外，本研究还表明，源自DFTD癌细胞的热休克蛋白具有免疫原性，为基于HSP的DFTD疫苗的进一步开发提供了支持。