肿瘤细胞治疗研究
英文原题：Leukemia's Next Top Model? Syngeneic Models to Advance Adoptive Cellular Therapy.
近年来，人们着重于利用免疫系统进行治疗干预。
近年来，人们一直强调利用免疫系统进行治疗干预。过继性细胞疗法（ACT）已成为B细胞衍生血液恶性肿瘤的有效选择。尽管ACT取得了显著成功，但免疫失调和白血病微环境可严重影响临床反应。因此，临床前建模有助于推动白血病ACT的进展。人源异种移植模型是目前ACT体内模型的主要支柱，但无法评估免疫抑制性白血病微环境对过继转移细胞的影响。同基因小鼠模型利用小鼠肿瘤模型并将其植入免疫健全小鼠中。这提供了一种替代模型，减少了复杂繁育策略的需求，同时保持了匹配的免疫系统、基质微环境和白血病负荷。评估ACT的同基因模型已分析了细胞毒性T淋巴细胞、T细胞受体转基因和嵌合抗原受体的复杂性。本综述探讨了白血病微环境的免疫抑制特征，讨论了临床前建模如何帮助预测ACT相关毒性和功能障碍，并探讨了在ACT研究中采用同基因建模以改进白血病疗法的文献。
In recent years, there has been an emphasis on harnessing the immune system for therapeutic interventions. Adoptive cell therapies (ACT) have emerged as an effective option for B-cell derived hematological malignancies. Despite remarkable successes with ACT, immune dysregulation and the leukemia microenvironment can critically alter clinical responses. Therefore, preclinical modeling can contribute to the advancement of ACT for leukemias. Human xenografts, the current mainstay of ACT in vivo models, cannot evaluate the impact of the immunosuppressive leukemia microenvironment on adoptively transferred cells. Syngeneic mouse models utilize murine tumor models and implant them into immunocompetent mice. This provides an alternative model, reducing the need for complicated breeding strategies while maintaining a matched immune system, stromal compartment, and leukemia burden. Syngeneic models that evaluate ACT have analyzed the complexity of cytotoxic T lymphocytes, T cell receptor transgenics, and chimeric antigen receptors. This review examines the immunosuppressive features of the leukemia microenvironment, discusses how preclinical modeling helps predict ACT associated toxicities and dysfunction, and explores publications that have employed syngeneic modeling in ACT studies for the improvement of therapy for leukemias.
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