Mesiano Giulia, Leuci Valeria, Giraudo Lidia, Gammaitoni Loretta, Carnevale Schianca Fabrizio, Cangemi Michela, Rotolo Ramona, Capellero Sonia, Pignochino Ymera, Grignani Giovanni, Aglietta Massimo, Sangiolo Dario
Candiolo Cancer Institute-IRCCS, Laboratory of Medical Oncology, Experimental Cell Therapy , Candiolo, Turin , Italy.
Expert Opin Biol Ther. 2015 Apr;15(4):517-28. doi: 10.1517/14712598.2015.987121. Epub 2014 Dec 16.
Conventional treatments reached an unsatisfactory therapeutic plateau in the treatment of advanced unresectable bone and soft tissue sarcomas that remain an unsolved medical need. Several evidences support the concept that adoptive immunotherapy may effectively integrate within the complex and multidisciplinary treatment of sarcomas.
In this work we reviewed adoptive immunotherapy strategies that have been explored in sarcoma settings, with specific focus on issues related to their clinic transferability. We schematically divided approaches based on T lymphocytes specific for MHC-restricted tumor-associated antigens or relying on MHC-independent immune effectors such as natural killer (NK), cytokine-induced killer (CIK) or γδ T cells.
Preclinical findings and initial clinical reports showed the potentialities and drawbacks of different adoptive immunotherapy strategies. The expansion of tumor infiltrating lymphocytes is difficult to be reproduced outside melanoma. Genetically redirected T cells appear to be a promising option and initial reports are encouraging against patients with sarcomas. Adoptive immunotherapy with MHC-unrestricted effectors such as NK, CIK or γδ T cells has recently shown great preclinical potential in sarcoma setting and biologic features that may favor clinical transferability. Combination of different immunotherapy approaches and integration with conventional treatments appear to be key issues for successful designing of next clinical trials.
在晚期不可切除的骨肉瘤和软组织肉瘤的治疗中，传统治疗方法已达到不尽人意的治疗平台期，这仍然是一个尚未解决的医学需求。多项证据支持过继性免疫疗法可有效融入肉瘤复杂多学科治疗的概念。
在这项工作中，我们回顾了在肉瘤背景下探索的过继性免疫疗法策略，特别关注与其临床可转化性相关的问题。我们根据针对MHC限制性肿瘤相关抗原的T淋巴细胞或依赖于MHC非依赖性免疫效应细胞（如自然杀伤细胞（NK）、细胞因子诱导杀伤细胞（CIK）或γδT细胞）的方法进行了示意性划分。
临床前研究结果和初步临床报告显示了不同过继性免疫疗法策略的潜力和缺点。肿瘤浸润淋巴细胞的扩增在黑色素瘤以外难以重现。基因重定向T细胞似乎是一个有前景的选择，针对肉瘤患者的初步报告令人鼓舞。使用NK、CIK或γδT细胞等MHC非限制性效应细胞的过继性免疫疗法最近在肉瘤背景下显示出巨大的临床前潜力以及可能有利于临床可转化性的生物学特性。不同免疫疗法方法的联合以及与传统治疗的整合似乎是成功设计下一轮临床试验的关键问题。
