Therapeutic strategy for hepatocellular carcinoma by dendritic cell-based tumor vaccination

基于树突状细胞的肿瘤疫苗接种治疗肝细胞癌的策略

• 批准号: 12557054
• 负责人: HAYASHI Norio
• 金额: $ 8.06万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12557054/
• 关键词: Tumor vaccine; Hepatocellular carcinoma; Dendritic cell; Immunogene therapy; Interleukin 12; 4-1 BB ligand; B7-1

Dendritic cells (DC) are potent antigen-presenting cells that are capable of priming systemic antitumor immune response. Here, we evaluated the combined effectiveness of tumor lysate-pulsed DC immunization and interleukin-12 (IL-12) administration on the induction of antitumor immunity in mouse hepatocellular carcinoma (HCC) model. Mouse DC were pulsed with lysate of BNL 1MB A.7R.1(BNL), a BALB/c-derived HCC cell line, and then injected into syngeneic mice in combination with systemic administration of IL-12. Lymphocytes from mice treated with BNL lysate-pulsed DC and IL-12 showed stronger cytolytic activity and produced higher amounts of IFNγ than those from mice treated with BNL lysate-pulsed DC alone. Although immunization with BNL lysate-pulsed DC alone did not lead to complete regression of established tumors, it significantly inhibited tumor growth compared with vehicle injection. Importantly, the combined therapy of BNL lysate-pulsed DC and IL-12 resulted in tumor rejection or significant inhibition of tumor growth compared with mice treated with BNL lysate-pulsed DC alone. In vivo lymphocyte depletion experiments demonstrated that this combination was dependent on both CD8^+ and CD4^+ T cells, but not NK cells. These results demonstrated that IL-12 administration enhanced the therapeutic effect of immunization of tumor lysate-pulsed DC against HCC in mice. This combination of IL-12 and DC may be useful for suppressing growth of residual tumor after primary therapy of human HCC.

树突状细胞（DC）是一种强有力的抗原提呈细胞，能够引发全身抗肿瘤免疫应答。在这里，我们评估了肿瘤裂解物脉冲的DC免疫和白细胞介素-12（IL-12）的管理在小鼠肝细胞癌（HCC）模型中诱导抗肿瘤免疫的联合有效性。小鼠DC用BNL 1 MB A.7R.1（BNL）（一种BALB/c衍生的HCC细胞系）的裂解物脉冲，然后与全身施用IL-12组合注射到同基因小鼠中。来自用BNL裂解物脉冲的DC和IL-12处理的小鼠的淋巴细胞显示出比来自仅用BNL裂解物脉冲的DC处理的小鼠的淋巴细胞更强的细胞溶解活性，并且产生更高量的IFNγ。虽然单独用BNL裂解物脉冲的DC免疫不能导致已建立的肿瘤完全消退，但与载体注射相比，它显著抑制肿瘤生长。重要的是，与单独用BNL裂解物脉冲的DC治疗的小鼠相比，BNL裂解物脉冲的DC和IL-12的联合治疗导致肿瘤排斥或肿瘤生长的显著抑制。体内淋巴细胞耗竭实验表明，这种组合依赖于CD 8 ^+和CD 4 ^+ T细胞，而不是NK细胞。这些结果表明，IL-12给药增强了肿瘤裂解物脉冲的DC免疫小鼠对HCC的治疗效果。IL-12和DC的这种组合可能有助于抑制人HCC初次治疗后残留肿瘤的生长。

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