研究概要
免疫疗法的出现彻底改变了癌症治疗。
中文摘要
免疫疗法的出现彻底改变了癌症治疗。然而,免疫检查点抑制剂的应用可能带来严重的副作用,并存在治疗耐药的风险。嵌合抗原受体(CAR)T细胞或CAR-NK细胞的制备需要专门的分子实验室,成本高昂,且难以适应快速增长癌症患者数量。为了提供一种更简单但有效的免疫疗法,基于紫外线C(UVC)照射的4T1三阴性乳腺癌细胞建立了全细胞肿瘤疫苗方案。使用刃天青和Annexin V/碘化丙啶流式细胞术检测验证了UVC照射后肿瘤细胞的凋亡。在免疫的BALB/c小鼠中实现了保护性免疫,显示部分缓解。来自缓解小鼠的脾细胞或血浆的过继转移在接受活4T1肿瘤细胞注射的初始BALB/c小鼠中显示出保护效果。在全细胞疫苗免疫后,小鼠血浆中记录了4T1特异性IgG抗体。使用白细胞介素-2(IL-2)和寡核苷酸2006(ODN2006)佐剂将C57BL/6小鼠的脾细胞转移到环磷酰胺处理的BALB/c小鼠中,导致生存期延长、肿瘤生长减少,并在33%的病例中实现缓解,且未发生移植物抗宿主病。我们的方法提供了一种简单、成本效益高的全细胞疫苗方案,可施用于免疫功能健全的健康生物体。血浆或HLA匹配的免疫供体来源白细胞的过继转移可用作癌症患者的免疫细胞疗法。
展开英文摘要原文
The advent of immunotherapy has revolutionized cancer treatments. However, the application of immune checkpoint inhibitors may entail severe side effects, with the risk of therapeutic resistance. The generation of chimeric antigen receptor (CAR) T-cells or CAR-NK cells requires specialized molecular laboratories, is costly, and is difficult to adapt to the rapidly growing number of cancer patients. To provide a simpler but effective immune therapy, a whole-cell tumor vaccine protocol was established based on ultraviolet C (UCV)-irradiated 4T1 triple-negative breast cancer cells. The apoptosis of tumor cells after UVC irradiation was verified using resazurin and Annexin V/propidium iodide flow cytometric assays. Protective immunity was achieved in immunized BALB/c mice, showing partial remission. Adoptive transfer of splenocytes or plasma from the mice in remission showed a protective effect in the naive BALB/c mice that received a living 4T1 tumor cell injection. 4T1-specific IgG antibodies were recorded in the plasma of the mice following immunization with the whole-cell vaccine. Interleukin-2 (IL-2) and oligonucleotide 2006 (ODN2006) adjuvants were used for the transfer of splenocytes from C57BL/6 mice into cyclophosphamide-treated BALB/c mice, resulting in prolonged survival, reduced tumor growth, and remission in 33% of the cases, without the development of the graft-versus-host disease. Our approach offers a simple, cost-effective whole-cell vaccine protocol that can be administered to immunocompetent healthy organisms. The plasma or the adoptive transfer of HLA-matching immunized donor-derived leukocytes could be used as an immune cell therapy for cancer patients.
论文信息
- 作者
- Szebeni GJ、Alföldi R、Nagy LI、Neuperger P、Gémes N、Balog JÁ、Tiszlavicz L、Puskás LG
- 单位
- Laboratory of Functional Genomics, Biological Research Centre, Temesvári krt. 62, H6726 Szeged, Hungary.Hungary
- 期刊
- Vaccines2023 Jul 18