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一种新型的肝癌免疫疗法:转染 AFPmRNA 的 CD40 激活 B 淋巴细胞。

A novel immunotherapy to hepatocellular carcinoma: CD40-activated B lymphocytes transfected with AFPmRNA.

机构信息

Department of General surgery, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China.

出版信息

Med Hypotheses. 2009 Nov;73(5):835-7. doi: 10.1016/j.mehy.2008.12.050. Epub 2009 Jul 25.

Abstract

Alpha-fetoprotein (AFP) is overexpressed in the majority of hepatocellular carcinomas (HCCs), and thus may offer attractive target for immunotherapy against this neoplasm. CD40 ligand (CD40L) is the major signal that induces B cells to efficiently present antigen to T cells, and CD40-activated B (CD40-B) lymphocyte cells may boost cytotoxic T lymphocytes (CTLs) when they are pulsed with tumour antigens. CTL is considered to be a promising therapeutic means for the treatment of cancers. Here, we intend to build a plasmid pGEM4Z/AFP/A64 and to prepare AFPmRNA, then separate B lymphocyte cells. These CD40-B cells are pulsed with AFPmRNA, and they may boost robust T-cell responses, but more importantly, they also may prime naive T-cell responses against hepatocarcinoma. These CD40-B cells will be a powerful source of APCs generated by simple and reliable technology that may be applied to antigen responses, immune treatment for cancer, vaccination approaches, and ex vivo T-cell expansion for adoptive therapy. AFPmRNA-transfected B cells may represent a broadly applicable vaccine strategy to induce potentially therapeutic CTL responses against AFP-positive target cells in HCC. Vaccine strategies such as these may contribute to the effective future treatment of HCC.

摘要

甲胎蛋白(AFP)在大多数肝癌(HCC)中过度表达,因此可能为针对这种肿瘤的免疫治疗提供有吸引力的靶标。CD40 配体(CD40L)是诱导 B 细胞向 T 细胞有效呈递抗原的主要信号,当用肿瘤抗原冲击时,CD40 激活的 B(CD40-B)淋巴细胞可以增强细胞毒性 T 淋巴细胞(CTL)。CTL 被认为是治疗癌症的一种很有前途的治疗手段。在这里,我们打算构建一个 pGEM4Z/AFP/A64 质粒,并准备 AFPmRNA,然后分离 B 淋巴细胞。这些 CD40-B 细胞用 AFPmRNA 冲击,可能会增强强烈的 T 细胞反应,但更重要的是,它们还可能针对肝癌诱导原始 T 细胞反应。这些 CD40-B 细胞将是一种强大的 APC 来源,通过简单可靠的技术产生,可应用于抗原反应、癌症免疫治疗、疫苗接种方法以及过继性治疗的体外 T 细胞扩增。转染 AFPmRNA 的 B 细胞可能代表一种广泛适用的疫苗策略,可诱导针对 AFP 阳性靶细胞的潜在治疗性 CTL 反应在 HCC 中。这种疫苗策略可能有助于 HCC 的有效未来治疗。

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