电穿孔(EP)介导的 DNA 疫苗在已建立的肿瘤模型中增强了异体淋巴细胞的抗肿瘤疗效。

IF 4.6 2区 医学 Q2 IMMUNOLOGY Cancer Immunology, Immunotherapy Pub Date : 2024-10-03 DOI:10.1007/s00262-024-03838-8
Sanyuan Shi, Luchen Zhang, Anjie Zheng, Fang Xie, Samuel Kesse, Yang Yang, Jinliang Peng, Yuhong Xu
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引用次数: 0

摘要

背景:肿瘤反应性 T 细胞在抗肿瘤反应中起着至关重要的作用,但 DNA 疫苗接种诱导的 T 细胞需要耗费大量时间,且抗肿瘤效果有限。因此,我们评估了电穿孔(EP)介导的针对表皮生长因子受体变异体 III 的 DNA 疫苗(pEGFRvIII 质粒)诱导的反应性 T 细胞的抗肿瘤效果,同时还评估了采用细胞疗法(ACT),即从接种了 pEGFRvIII EP 疫苗的健康供体中转移淋巴细胞:方法:通过免疫荧光和 Western 印迹分析确认了已建立的 pEGFRvIII 质粒和 EGFRvIII 阳性细胞模型。流式细胞术和细胞毒性试验评估了 EP 介导的 pEGFRvIII 疫苗、ACT 或它们的组合诱导的抗原特异性反应 T 细胞的功能。在B16F10-EGFRvIII肿瘤模型中评估了EP介导的pEGFRvIII疫苗单独使用或与ACT联合使用的抗肿瘤效果:结果:EP介导的 pEGFRvIII 疫苗可在健康小鼠和肿瘤小鼠体内激发血清抗体和强大的细胞免疫反应。然而,在已建立的肿瘤模型中,这种反应只能在一定程度上抑制早期肿瘤的生长。EP介导的pEGFRvIII疫苗接种后,再采用接种过疫苗的健康供体的淋巴细胞进行转移,可获得显著的抗肿瘤疗效,这归功于ACT补充的抗原特异性CD4+ Th1细胞和EP介导的DNA疫苗接种激发的抗原特异性CD8+ T细胞的协同作用:我们的临床前研究结果表明,EP介导的DNA疫苗接种与被收养转移、接种健康供体来源的异体淋巴细胞协同作用,可增强抗肿瘤疗效。
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Enhanced anti-tumor efficacy of electroporation (EP)-mediated DNA vaccine boosted by allogeneic lymphocytes in pre-established tumor models.

Background: Tumor-reactive T cells play a crucial role in anti-tumor responses, but T cells induced by DNA vaccination are time-consuming processes and exhibit limited anti-tumor efficacy. Therefore, we evaluated the anti-tumor effectiveness of reactive T cells elicited by electroporation (EP)-mediated DNA vaccine targeting epidermal growth factor receptor variant III (pEGFRvIII plasmid), in conjunction with adoptive cell therapy (ACT), involving the transfer of lymphocytes from a pEGFRvIII EP-vaccinated healthy donor.

Methods: The validation of the established pEGFRvIII plasmid and EGFRvIII-positive cell model was confirmed through immunofluorescence and western blot analysis. Flow cytometry and cytotoxicity assays were performed to evaluate the functionality of antigen-specific reactive T cells induced by EP-mediated pEGFRvIII vaccines, ACT, or their combination. The anti-tumor effectiveness of EP-mediated pEGFRvIII vaccines alone or combined with ACT was evaluated in the B16F10-EGFRvIII tumor model.

Results: EP-mediated pEGFRvIII vaccines elicited serum antibodies and a robust cellular immune response in both healthy and tumor-bearing mice. However, this response only marginally inhibited early-stage tumor growth in established tumor models. EP-mediated pEGFRvIII vaccination followed by adoptive transfer of lymphocytes from vaccinated healthy donors led to notable anti-tumor efficacy, attributed to the synergistic action of antigen-specific CD4+ Th1 cells supplemented by ACT and antigen-specific CD8+ T cells elicited by the EP-mediated DNA vaccination.

Conclusions: Our preclinical studies results demonstrate an enhanced anti-tumor efficacy of EP-mediated DNA vaccination boosted with adoptively transferred, vaccinated healthy donor-derived allogeneic lymphocytes.

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来源期刊
CiteScore
10.50
自引率
1.70%
发文量
207
审稿时长
1 months
期刊介绍: Cancer Immunology, Immunotherapy has the basic aim of keeping readers informed of the latest research results in the fields of oncology and immunology. As knowledge expands, the scope of the journal has broadened to include more of the progress being made in the areas of biology concerned with biological response modifiers. This helps keep readers up to date on the latest advances in our understanding of tumor-host interactions. The journal publishes short editorials including "position papers," general reviews, original articles, and short communications, providing a forum for the most current experimental and clinical advances in tumor immunology.
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