Department of Clinical Sciences, North Carolina State University College of Veterinary Medicine, Raleigh, North Carolina, USA.
Precision Biosciences, Durham, North Carolina, USA.
HLA. 2021 May;97(5):428-434. doi: 10.1111/tan.14197. Epub 2021 Feb 18.
Canine spontaneous cancers may offer greater fidelity than rodent models in advancing clinical immunotherapies. Boxers in particular are distinguished as study subjects by their popularity, and high incidence of human-relevant cancers. Further, the MHC class I allele DLA-88034:01, with a known motif, dominates the breed, facilitating discovery of shared CTL responses against mutation-origin neoepitopes by standard prediction methods. We experimentally confirmed the allomorph's binding motif by developing an MHC surface stabilization assay. The assay validated four DLA-88034:01-presented peptides from canine distemper virus, ubiquitously administered in routine vaccines, for positive controls in future CTL studies. In turn, these viral peptides substantiated motif-based prediction for DLA-88*034:01. The study adds new tools for studying neoepitope-specific CTL in Boxers to foster canine comparative oncology.
犬自发性肿瘤在推进临床免疫疗法方面可能比啮齿动物模型更具可信度。特别是拳师犬因其受欢迎程度和高发的人类相关癌症而成为研究对象。此外,具有已知基序的 MHC Ⅰ类等位基因 DLA-88034:01 在该品种中占主导地位,这有助于通过标准预测方法发现针对突变起源的新表位的共同 CTL 反应。我们通过开发 MHC 表面稳定测定法来实验性地证实了同种异体的结合基序。该测定法验证了犬瘟热病毒的四种 DLA-88034:01 呈递肽,这些肽在常规疫苗中广泛施用,可作为未来 CTL 研究的阳性对照肽。反过来,这些病毒肽证实了 DLA-88*034:01 的基于基序的预测。该研究为研究拳师犬中新型表位特异性 CTL 提供了新工具,以促进犬科比较肿瘤学的发展。