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黑色素瘤的肿瘤浸润淋巴细胞疗法:原理及进一步临床开发的问题

Tumor-infiltrating lymphocyte therapy for melanoma: rationale and issues for further clinical development.

作者信息

Sim Geok Choo, Chacon Jessica, Haymaker Cara, Ritthipichai Krit, Singh Manish, Hwu Patrick, Radvanyi Laszlo

机构信息

Department of Melanoma Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Box 904, 1515 Holcombe Boulevard, Houston, TX, 77030, USA.

出版信息

BioDrugs. 2014 Oct;28(5):421-37. doi: 10.1007/s40259-014-0097-y.

Abstract

Cancer immunotherapy has become an important area for the future development of cancer therapy; this includes T-cell-based therapies that involve adoptive transfer of autologous T cells derived from the tumors or peripheral blood of cancer patients, vaccines, oncolytic virus therapy, and immunomodulatory antibodies and ligands. Here, we summarize the current approaches and clinical data in the field of adoptive T-cell transfer therapy using tumor-infiltrating lymphocytes (TILs) for metastatic melanoma. We also discuss current knowledge on the mechanism of transferred TILs in mediating tumor regression and the growing need for and recent advances in the identification of predictive biomarkers to better select patients for TIL therapy. The current technical limitations of current TIL expansion methods for out-scaling are discussed as well as how these are being addressed in order to further "industrialize" this form of cell therapy. Lastly, how TIL adoptive transfer can be incorporated into the current melanoma treatment continuum, especially as combination therapy with other immunomodulators and targeted drugs, is discussed.

摘要

癌症免疫疗法已成为癌症治疗未来发展的一个重要领域;这包括基于T细胞的疗法,涉及过继性转移源自癌症患者肿瘤或外周血的自体T细胞、疫苗、溶瘤病毒疗法以及免疫调节抗体和配体。在此,我们总结了使用肿瘤浸润淋巴细胞(TILs)治疗转移性黑色素瘤的过继性T细胞转移疗法领域的当前方法和临床数据。我们还讨论了关于转移的TILs介导肿瘤消退机制的当前知识,以及对预测性生物标志物进行鉴定以更好地选择TIL疗法患者的需求不断增加和近期进展。讨论了当前TIL扩增方法在扩大规模方面的技术局限性,以及如何解决这些问题以进一步将这种细胞疗法“产业化”。最后,讨论了TIL过继性转移如何纳入当前黑色素瘤治疗的连续过程,特别是作为与其他免疫调节剂和靶向药物的联合疗法。

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