决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Role of companion dogs in cancer immunotherapy development.
用于评估新型癌症免疫疗法的啮齿动物模型往往无法完全再现癌症患者体内发生的免疫相互作用的复杂性。
用于评估新型癌症免疫疗法的啮齿动物模型往往无法完全再现癌症患者体内发生的免疫相互作用的复杂性。患有自发癌症的伴侣犬在免疫学上比啮齿动物更接近人类。这种相似性部分是因为它们的免疫系统在早期通过反复接种疫苗以及病毒和细菌感染得到了教育,随后在生命后期又被通常需要数月才能发展成型的肿瘤进一步塑造。此外,犬类在循环系统和肿瘤组织内均具备人类存在的所有主要白细胞亚群。与评估新型癌症免疫疗法最相关的主要犬类癌症模型包括骨肉瘤、胶质瘤、非霍奇金淋巴瘤、黑色素瘤、尿路上皮癌和头颈癌。这些癌症中的每一种都在不同程度上再现了人类类似癌症的遗传学、组织学和生物学行为。在伴侣犬中正在积极研究的免疫疗法包括CAR-T 细胞疗法、髓系细胞靶向疗法、放射免疫疗法和肿瘤疫苗。这些正在进行的研究结果有望加速有前景的疗法组合向人类的转化,同时也能识别出无效或与不可接受的免疫毒性相关的方法。
Rodent models for evaluating new cancer immunotherapies often fail to fully recapitulate the complexity of immune interactions that occur in cancer patients. Companion dogs with spontaneously developing cancers more closely resemble humans immunologically than rodents. This resemblance results in part because their immune systems have been educated early by repeated vaccinations and viral and bacterial infections, with further sculpting later in life by tumors that typically take months to develop. Moreover, dogs possess all of the major leukocyte subsets present in humans, both in circulation and within tumor tissues. The major canine cancer models most relevant to evaluating new cancer immunotherapies include osteosarcoma, glioma, non-Hodgkin lymphoma, melanoma, uroepithelial cancer, and head and neck cancers. Each of these cancers recapitulates to varying degrees the genetics, histology, and biological behaviors of the human analogous cancers. Immune therapies under active investigation in companion dogs include chimeric antigen receptor T-cell therapies, myeloid cell-targeted therapies, radioimmunotherapy, and tumor vaccines. Results of these ongoing studies are expected to accelerate the translation to humans of promising therapy combinations, while also identifying approaches that are ineffective or associated with unacceptable immunological toxicities.
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