Cytokine Modification of Adoptive Chimeric Antigen Receptor Immunotherapy for Glioblastoma.
Cytokine Modification of Adoptive Chimeric Antigen Receptor Immunotherapy for Glioblastoma.
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胶质母细胞瘤嵌合抗原受体免疫治疗的细胞因子修饰。
DOI：
10.3390/cancers15245852
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发表时间：
2023-12-15
期刊：
影响因子：
5.2
通讯作者：
Balyasnikova, Irina V.
中科院分区：
文献类型：
--
作者：
Pawlowski, Kristen D.;Duffy, Joseph T.;Gottschalk, Stephen;Balyasnikova, Irina V.
嵌合抗原受体(CAR)细胞治疗胶质母细胞瘤是一种很有前途的治疗方法，胶质母细胞瘤是一种治疗选择有限的致命脑癌。目前正在努力改进这些疗法，其中一种方法是细胞因子修饰。细胞因子是体内细胞产生的一种蛋白质，可以改变免疫细胞的功能。在这篇综述中，作者总结了使用细胞因子来改进CAR细胞治疗的方法。这些措施包括将CAR T细胞或CAR NK细胞与细胞因子、抗体或溶瘤病毒联合使用，或通过工程CAR细胞疗法来分泌或表达细胞因子，表达细胞因子受体，或从基因上改变细胞因子信号通路。我们希望，为CAR细胞治疗提供细胞因子支持将提高其对胶质母细胞瘤患者的疗效。嵌合抗原受体(CAR)细胞为基础的治疗在实体肿瘤中的成功有限，包括胶质母细胞瘤(GBM)。基底膜表现出高度的异质性，并创造了免疫抑制的肿瘤微环境(TME)。此外，CAR治疗还存在其他挑战，包括贩运和渗透到肿瘤部位、增殖、一旦进入肿瘤就持续存在，以及功能降低，如细胞因子产生不佳。细胞因子的修饰很有意义，因为通过直接将CAR疗法与改变细胞因子反应途径的细胞因子、抗体或溶瘤病毒相结合，可以提高治疗效果并将非靶点毒性降至最低。或者，人们可以通过基因修饰CAR T细胞或CAR NK细胞来分泌细胞因子或表达细胞因子或细胞因子受体。最后，可以对CARS进行基因改造，以增强或抑制细胞内细胞因子信号通路，从而实现更直接的方法。细胞因子与CARS联合传递是最直接的方法，但它有相关的毒性。或者，CAR治疗与抗体(如抗IL-6、抗PD1和抗VEGF)或溶瘤病毒相结合，可增强CAR细胞对GBM肿瘤的侵袭，并向TME提供促炎信号。分泌细胞因子(如IL-12、IL-15和IL-18)的CAR T或NK细胞在多种GBM亚型中表现出更好的疗效。同样，在CAR细胞中表达促进或抑制细胞因子信号的细胞因子调节受体也增强了它们的活性。最后，人们正在积极寻求基因编辑方法，以直接影响汽车细胞中的免疫信号通路。在这篇综述中，我们总结了这些细胞因子的修饰方法，并强调了存在的任何差距，以期促进基于CAR的胶质母细胞瘤治疗的改进。
Chimeric antigen receptor (CAR) cell-based therapy is a promising treatment approach for glioblastoma, a fatal brain cancer with limited treatment options. Efforts to improve these therapies are currently underway, with one method being cytokine modification. Cytokines are a type of protein created by cells in the body that can change the function of immune cells. In this review, the authors summarize approaches that employ cytokines to improve CAR cell therapies. These include coadministering CAR T-cells or CAR NK-cells with cytokines, antibodies, or oncolytic viruses or via engineering CAR cell therapies to secrete or express cytokines, express a cytokine receptor, or genetically alter cytokine signaling pathways. We hope that providing cytokine support to CAR cell-based therapies will improve their efficacy for patients with glioblastoma. Chimeric antigen receptor (CAR) cell-based therapies have demonstrated limited success in solid tumors, including glioblastoma (GBM). GBMs exhibit high heterogeneity and create an immunosuppressive tumor microenvironment (TME). In addition, other challenges exist for CAR therapy, including trafficking and infiltration into the tumor site, proliferation, persistence of CARs once in the tumor, and reduced functionality, such as suboptimal cytokine production. Cytokine modification is of interest, as one can enhance therapy efficacy and minimize off-target toxicity by directly combining CAR therapy with cytokines, antibodies, or oncolytic viruses that alter cytokine response pathways. Alternatively, one can genetically modify CAR T-cells or CAR NK-cells to secrete cytokines or express cytokines or cytokine receptors. Finally, CARs can be genetically altered to augment or suppress intracellular cytokine signaling pathways for a more direct approach. Codelivery of cytokines with CARs is the most straightforward method, but it has associated toxicity. Alternatively, combining CAR therapy with antibodies (e.g., anti-IL-6, anti-PD1, and anti-VEGF) or oncolytic viruses has enhanced CAR cell infiltration into GBM tumors and provided proinflammatory signals to the TME. CAR T- or NK-cells secreting cytokines (e.g., IL-12, IL-15, and IL-18) have shown improved efficacy within multiple GBM subtypes. Likewise, expressing cytokine-modulating receptors in CAR cells that promote or inhibit cytokine signaling has enhanced their activity. Finally, gene editing approaches are actively being pursued to directly influence immune signaling pathways in CAR cells. In this review, we summarize these cytokine modification methods and highlight any existing gaps in the hope of catalyzing an improved generation of CAR-based therapies for glioblastoma.
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影响因子：
11.2
作者：
Hardee ME;Marciscano AE;Medina-Ramirez CM;Zagzag D;Narayana A;Lonning SM;Barcellos-Hoff MH
通讯作者：
Barcellos-Hoff MH
增强胶质母细胞瘤的汽车T细胞疗法的前瞻性方法。
影响因子：
7.3
作者：
通讯作者：
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影响因子：
6.2
作者：
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通讯作者：
Kirkwood JM
影响因子：
5.2
作者：
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通讯作者：
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影响因子：
11.5
作者：
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通讯作者：
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