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免疫治疗的转化靶标:从宠物犬到人。

Translational oncotargets for immunotherapy: From pet dogs to humans.

机构信息

CIISA, Centro de Investigação Interdisciplinar em Sanidade Animal, Faculdade de Medicina Veterinária, Universidade de Lisboa, Av. da Universidade Técnica, 1300-477 Lisboa, Portugal.

EnviHeB Lab, Instituto de Saúde Ambiental, Faculdade de Medicina, Universidade de Lisboa, Av. Professor Egas Moniz, 1649-028 Lisboa, Portugal.

出版信息

Adv Drug Deliv Rev. 2021 May;172:296-313. doi: 10.1016/j.addr.2021.02.020. Epub 2021 Mar 9.

Abstract

Preclinical studies in rodent models have been a pivotal role in human clinical research, but many of them fail in the translational process. Spontaneous tumors in pet dogs have the potential to bridge the gap between preclinical models and human clinical trials. Their natural occurrence in an immunocompetent system overcome the limitations of preclinical rodent models. Due to its reasonable cellular, molecular, and genetic homology to humans, the pet dog represents a valuable model to accelerate the translation of preclinical studies to clinical trials in humans, actually with benefits for both species. Moreover, their unique genetic features of breeding and breed-related mutations have contributed to assess and optimize therapeutics in individuals with different genetic backgrounds. This review aims to outline four main immunotherapy approaches - cancer vaccines, adaptive T-cell transfer, antibodies, and cytokines -, under research in veterinary medicine and how they can serve the clinical application crosstalk with humans.

摘要

啮齿动物模型的临床前研究在人类临床研究中起着关键作用,但其中许多在转化过程中失败了。宠物犬的自发性肿瘤有可能弥合临床前模型和人类临床试验之间的差距。它们在免疫功能正常的系统中自然发生,克服了临床前啮齿动物模型的局限性。由于宠物犬与人类在细胞、分子和遗传上具有合理的同源性,因此它代表了一种有价值的模型,可以加速将临床前研究转化为人类临床试验,实际上对两种物种都有好处。此外,它们独特的繁殖遗传特征和与品种相关的突变有助于评估和优化不同遗传背景个体的治疗方法。这篇综述旨在概述兽医研究中正在研究的四种主要免疫疗法方法——癌症疫苗、适应性 T 细胞转移、抗体和细胞因子——以及它们如何为与人类的临床应用交流提供服务。

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