Evaluation of antitumor immunity and paraneoplastic neurological syndrome evoked by murine dendritic cells pulsed with HuD antigen.

HuD 抗原脉冲的鼠树突状细胞引起的抗肿瘤免疫和副肿瘤神经综合征的评估。

• 批准号: 12670576
• 负责人: OHWADA Akihiko
• 金额: $ 2.05万
• 依托单位: JUNTENDO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 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/grant/KAKENHI-PROJECT-12670576/
• 关键词: HuD antigen; small cell lung cancer; granulysin; Dendritic cells; CD3陽性細胞

There is a clinically significant correlation between the presence of an antibody against the paraneoplastic encephalomyelitis antigen HuD (HuD antigen) and limitation of tumor spread in patients with small cell lung cancer (SCLC). The dendritic cells pulsed with tumor specific antigen such as HuD antigen will potentate the cellular immunity against the tumors. The expression of HuD antigen was evaluated by Western blotting in the murine splenic dendritic cells infected with HuD antigen expressing adenovirus vector. However, the expression of HuD antigen was not detectable by western blotting in the cells infected with our HuD-expressing adenovirus vector even at 50 moi (multiplicity of infection). Next we evaluated the effects of granulysin, a tumorcidal molecule secreted by cytotoxic T cells (CTL) and natural killer (NK) cells in HuD antigen-expressing small cell lung cancer murine model cells (Colon 26/HuD) infected with granulysin expressing adenovirus vector. Adenovirus vector-mediated transfer of 9kDa granulysin increased DNA fragmentation in Colon 26/HuD cells 2.5-fold and suppressed 21% of the Colon 26/HuD proliferation on day 3 (p<0.05 for each value) after the transfer of granulysin, compared with the control adenovirus vector transfer. In contract, adenovirus vector-mediated transfer of 9kDa granulysin did not increase DNA fragmentation nor suppress the proliferation of Colon 26 parent cells. The sensitivity of HuD-expressing tumor cells to granulysin is likely to partially explain the susceptibility of SCLC to cell-mediated immunity. These results support that HuD antigen is still good candidate molecule for antitumor immunity against SCLC and propose to evaluate the anti-tumor effect of dendritic cells pulsed with recombinant HuD antigen.

抗副肿瘤性脑脊髓炎抗原HUD(HUD抗原)抗体的存在与小细胞肺癌(SCLC)患者肿瘤扩散受限之间存在显著的临床相关性。用肿瘤特异性抗原如HUD抗原冲击的树突状细胞将增强抗肿瘤的细胞免疫。用免疫印迹法检测表达HUD抗原的腺病毒载体感染小鼠脾树突状细胞后HUD抗原的表达。然而，在表达HUD的腺病毒载体感染的细胞中，即使在50MOI(感染的多样性)的情况下，Western blotting也没有检测到HUD抗原的表达。接下来，我们观察了细胞毒性T细胞(CTL)和自然杀伤细胞(NK)分泌的杀瘤分子颗粒溶素对表达HUD抗原的小细胞肺癌小鼠模型细胞(COLON 26/HUD)感染颗粒溶素的作用。与对照组相比，腺病毒载体介导的9 kDa颗粒溶素转染组在转染腺病毒后第3天，结肠26/HUD细胞的DNA片段化增加2.5倍，增殖抑制21%(p&lt；每个值0.05)。而腺病毒载体介导的9 kDa颗粒溶素转染组并没有增加DNA片段化，也没有抑制亲本细胞的增殖。表达HUD的肿瘤细胞对颗粒溶素的敏感性可能部分解释了小细胞肺癌对细胞免疫的敏感性。这些结果支持HUD抗原仍然是抗小细胞肺癌抗肿瘤免疫的良好候选分子，并建议评价重组HUD抗原冲击的树突状细胞的抗肿瘤效果。

项目成果

Nagaoka I et al.: "Synergistic actions of antibacterial neutrophil defensins and cathelicidins."Inflamm Res. 49. 73-9 (2000)

Nagaoka I 等人：“抗菌中性粒细胞防御素和抗菌素的协同作用。”Inflamm Res。

Sekiya M et al.: "Adenovirus vector-mediated transfer of 9kDa granulysin induces DNA fragmentation in HuD antigen-expressing small cell lung cancer murine model cells."Respirology. 7. 29-35 (2002)

Sekiya M 等人：“腺病毒载体介导的 9kDa 颗粒溶素转移在表达 HuD 抗原的小细胞肺癌小鼠模型细胞中诱导 DNA 片段化。”呼吸学。

Yoshioka Y, et al.: "Increased circulating CD16^+ CD14^<dim> monocytes in a patient with pulmonary alveolar proteinosis"Respirology. (in press). (2002)

Yoshioka Y 等人：“肺泡蛋白沉积症患者循环 CD16^ CD14^<dim> 单核细胞增加”呼吸学。

Yoshioka Y., et al.: "Increased circulating CD16^+ CDl4^<dim> monocytes in a patient with pulmonary alveolar proteinosis"Respirology. (in press). (2002)

Yoshioka Y.等人：“肺泡蛋白沉积症患者循环CD16^CD14^<dim>单核细胞增加”呼吸学。

Nagaoka I, et al.: "Synergistic actions of antibacterial neutrophil defensins and cathelicidins"Inflamm Res.. 49. 73-79 (2000)

Nagaoka I 等：“抗菌中性粒细胞防御素和抗菌肽的协同作用”Inflamm Res.. 49. 73-79 (2000)