肿瘤细胞治疗研究
英文原题：Selective expansion of anti-tumor innate lymphocytes in long-term cultures after a single BCG pulse.
自然杀伤（NK）细胞是参与识别病原体感染细胞和癌细胞的细胞毒性淋巴细胞。
自然杀伤（NK）细胞是参与识别病原体感染细胞和癌细胞的细胞毒性淋巴细胞。NK 细胞作为细胞治疗工具非常有吸引力，因为它们既不受供者相容性的限制，也不会引起毒性。尽管其抗肿瘤作用早已为人所知，但为了开发基于 NK 的疗法，选择适当的亚群非常重要。同样，非 MHC 限制性 T 细胞，特别是 γδ T 细胞，也被提出作为对抗癌症的新武器。在此，我们描述了一种生产和表征抗肿瘤先天淋巴细胞培养物的新方法，这些培养物主要包含 NK 和 γδ T 细胞，基于用 BCG（卡介苗），即结核病疫苗，刺激外周血单个核细胞（PBMC），BCG 也成功用于治疗非肌层浸润性膀胱癌。抗肿瘤先天淋巴细胞从 BCG 预刺激的 PBMC 中特异性增殖，并可在低剂量 IL12、IL15 和 IL21 中培养数周。这些细胞杀伤多种肿瘤，并在数周内保持功能，且操作最少。本文解释了通过多参数流式细胞术对这些培养物进行的表型分析。还描述了功能测定，包括淋巴细胞脱颗粒、细胞因子产生和无放射性同位素特异性裂解实验。
Natural Killer (NK) cells are cytotoxic lymphocytes involved in the recognition of pathogen-infected and cancer cells. NK cells are very attractive as cell therapy tools because they are neither restricted by donor compatibility nor do they cause toxicity. Although their anti-tumor role has been long known, for development of NK-based therapies it is important to select the appropriate subpopulation. Similarly, non-MHC restricted T cells, in particular γδ T cells, have also been proposed as novel weapons against cancer. Here, we describe a new approach for production and characterization of anti-tumor innate lymphocyte cultures, containing mainly NK and γδ T cells, based on stimulation of peripheral blood mononuclear cells (PBMC) with BCG (Bacillus Calmette-Guérin), the tuberculosis vaccine, which is also successfully used to treat non-muscle invasive bladder cancer. Anti-tumor innate lymphocytes specifically proliferate from BCG-primed PBMC and can be cultured for weeks in low doses of IL12, IL15 and IL21. These cells kill a wide range of tumors and remain functional for weeks, with minimal manipulation. The phenotypic analysis of these cultures by multi-parametric flow cytometry is explained. Functional assays, including lymphocyte degranulation, cytokine production and radioactive isotope-free specific lysis experiments are also described.
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