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首页> 外文期刊>Journal of immunotherapy >Manufacturing of large numbers of patient-specific T cells for adoptive immunotherapy: an approach to improving product safety, composition, and production capacity.
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Manufacturing of large numbers of patient-specific T cells for adoptive immunotherapy: an approach to improving product safety, composition, and production capacity.

机译：制造大量用于过继免疫疗法的患者特异性T细胞：一种提高产品安全性，成分和生产能力的方法。

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We have developed an innovative system for ex vivo processing of patient-specific cell products to produce large numbers of T-lymphocytes in support of phase 2 adoptive immunotherapy trials for hematologic malignancies. Extensive efforts were undertaken to close the cell processing system to improve the safety profile of the process and comply with new federal regulations regarding cell and tissue processing. Our results demonstrate that apheresis products can be processed in a closed system (Cytomate) with similar yields (approximately 4 x 10(9) mononuclear cells/apheresis) and recoveries (approximately 60% of starting mononuclear cells) to manual cell processing. Cells processed with this system could be cryopreserved for up to 5 months without significant loss of recovery or viability. Additionally, we have evaluated the use of gas permeable bags and developed perfusion bioreactor protocols in which T cells can be rapidly produced in excess of 10(10) viable cells per liter of culture. Using similar methods for upfront processing, we have also developed methods for positive selection and ex vivo culture of CD4+ T cells that result in 200 to 800-fold expansion of fresh or cryopreserved samples. T cells produced in these systems were shown to retain activation-induced cytolytic capability and TH1/TH2 cytokine production as a measure of biologic potency. These new methods allow for more efficient production multiple patient-specific products by satisfying the basic tenants of safety and efficacy required for early phase clinical trials of cell products.
机译：我们已经开发出一种创新的系统，用于离体加工患者特异性细胞产品以产生大量T淋巴细胞，以支持血液系统恶性肿瘤的2期过继免疫疗法试验。进行了广泛的努力以关闭细胞处理系统，以改善过程的安全性并遵守有关细胞和组织处理的新联邦法规。我们的结果表明，单采血液分离术产品可以在封闭系统（Cytomate）中以相似的产量（约4 x 10（9）个单核细胞/血浆）和回收率（约占起始单核细胞的60％）与手动细胞处理进行加工。用该系统处理过的细胞可以冷冻保存长达5个月，而不会显着降低恢复或活力。此外，我们评估了透气袋的使用并开发了灌注生物反应器方案，其中每升培养液可快速产生超过10（10）个活细胞的T细胞。使用类似的方法进行前处理，我们还开发了用于CD4 + T细胞阳性选择和离体培养的方法，可导致新鲜或冷冻保存的样品扩增200至800倍。在这些系统中产生的T细胞显示保留激活诱导的溶细胞能力和TH1 / TH2细胞因子的产生，作为生物学效能的量度。这些新方法通过满足细胞产品早期临床试验所需的安全性和有效性的基本租户，可以更有效地生产多种患者专用产品。

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