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Clinical Studies on Cytokine-Induced Killer Cells: Lessons from Lymphoma Trials

細(xì)胞因子誘導(dǎo)的殺傷細(xì)胞的臨床研究：淋巴瘤試驗(yàn)的教訓(xùn)

Lymphoma is a heterogeneous group of neoplasms including over 70 different subtypes. Its biological characteristic of deriving from lymphoid tissues makes it ideal for immunotherapy. In this paper, we provide insights into lymphoma-specific clinical trials based on cytokine-induced killer (CIK) cell therapy. We also reviewed pre-clinical lymphoma models where CIK cells have been used along with other synergetic tumor-targeting immune modules to improve their therapeutic potential. From a broader perspective, we will highlight that CIK cell therapy has potential, and in this rapidly evolving landscape of cancer therapies its optimization (as a personalized therapeutic approach) will be beneficial in lymphomas.

淋巴瘤是一組異質(zhì)性腫瘤，包括 70 多種不同的亞型。其源自淋巴組織的生物學(xué)特性使其成為免疫療法的理想選擇。在本文中，我們提供了對(duì)基于細(xì)胞因子誘導(dǎo)的殺傷 (CIK) 細(xì)胞療法的淋巴瘤特異性臨床試驗(yàn)的見解。我們還審查了臨床前淋巴瘤模型，其中 CIK 細(xì)胞已與其他協(xié)同腫瘤靶向免疫模塊一起使用，以提高其治療潛力。從更廣泛的角度來看，我們將強(qiáng)調(diào) CIK 細(xì)胞療法具有潛力，在這個(gè)快速發(fā)展的癌癥療法領(lǐng)域，其優(yōu)化（作為個(gè)性化治療方法）將有益于淋巴瘤。

5L高效搖瓶

CIK cells have demonstrated favorable safety profile and promising anti-tumor response in the 17 lymphoma-specific clinical trials. The improvements on its cytotoxicity will further make CIK cells an important tool in future therapeutic regimens. As GVHD is one of the most severe complications in donor lymphocyte infusion (DLI) after HSCT, CIK cells would be a favorable alternative to DLI due to its low allo-reactive potential. Besides, patients with central nervous system (CNS) pathology and declining performance status are usually not suitable for CAR-T therapy. CIK cells with mild toxicities would be one of the feasible options for the lymphoma patients after receiving two prior lines of therapy.

Considering that each lymphoma patient could benefit from individual therapy (as a personalized therapeutic approach), it is therefore important to stratify those subgroups that respond well to CIK cell therapy, and to understand the precise molecular mechanisms that support the functioning CIK cells in their disease state. As an initiative, the International Registry for CIK Cells (IRCC) has been established to collect clinical data worldwide and to set new standards for global reporting of clinical trials involving CIK cells [26,62,63]. On molecular grounds, lymphomas being heterogenous in nature may help to elucidate different factors (genetic, epigenetic, microenvironment, immunological etc.) that can improve the therapeutic effects of CIK cells. On a broader prospective, it can be concluded that CIK cell therapy has potential and in this rapidly evolving landscape of cancer therapies, optimizing CIK cell therapy in combination with other modules (as complementary rather than competitive) will be a crucial task in lymphomas.

10層細(xì)胞工廠

CIK 細(xì)胞在 17 項(xiàng)淋巴瘤特異性臨床試驗(yàn)中顯示出良好的安全性和有希望的抗腫瘤反應(yīng)。其細(xì)胞毒性的改進(jìn)將進(jìn)一步使 CIK 細(xì)胞成為未來治療方案中的重要工具。由于 GVHD 是 HSCT 后供體淋巴細(xì)胞輸注 (DLI) 中最嚴(yán)重的并發(fā)癥之一，CIK 細(xì)胞由于其低同種異體反應(yīng)潛力將成為 DLI 的有利替代品。此外，中樞神經(jīng)系統(tǒng)（CNS）病變和體能狀態(tài)下降的患者通常不適合CAR-T治療。具有輕度毒性的 CIK 細(xì)胞將是接受兩種先前治療后的淋巴瘤患者的可行選擇之一。

考慮到每個(gè)淋巴瘤患者都可以從個(gè)體治療中受益（作為一種個(gè)性化的治療方法），因此對(duì)那些對(duì) CIK 細(xì)胞治療反應(yīng)良好的亞組進(jìn)行分層，并了解支持其疾病中發(fā)揮功能的 CIK 細(xì)胞的精確分子機(jī)制是很重要的狀態(tài)。作為一項(xiàng)倡議，CIK 細(xì)胞國(guó)際注冊(cè)中心 (IRCC) 已成立，旨在收集全球臨床數(shù)據(jù)并為涉及 CIK 細(xì)胞的臨床試驗(yàn)的全球報(bào)告制定新標(biāo)準(zhǔn) [ 26 , 62 , 63]。在分子基礎(chǔ)上，淋巴瘤本質(zhì)上是異質(zhì)的，可能有助于闡明可以提高 CIK 細(xì)胞治療效果的不同因素（遺傳、表觀遺傳、微環(huán)境、免疫學(xué)等）。從更廣泛的角度來看，可以得出結(jié)論，CIK 細(xì)胞療法具有潛力，在這種快速發(fā)展的癌癥療法領(lǐng)域，優(yōu)化 CIK 細(xì)胞療法與其他模塊（作為補(bǔ)充而不是競(jìng)爭(zhēng)）相結(jié)合將是淋巴瘤的一項(xiàng)關(guān)鍵任務(wù)。

關(guān)鍵詞：lymphoma; cytokine-induced killer cells; clinical study; immunotherapy 淋巴瘤；細(xì)胞因子誘導(dǎo)的殺傷細(xì)胞；臨床研究；免疫療法

來源：MDPI https://www.mdpi.com/2072-6694/13/23/6007/htm