Development of tumor immunotherapy by vaccinated cancer cells

通过接种疫苗的癌细胞开发肿瘤免疫疗法

• 批准号: 05671655
• 负责人: UMEZU Yasuiki
• 金额: $ 1.47万
• 依托单位: TOHOKU University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05671655/
• 关键词: Human cancer cells; Immunogenicity; Ultraviolet-B irradiation; IL-2 gene-transduction; IL-12gene-transduction; MHC antigen; Cytotoxic TLymphocyte(CTL); NK-cells; Human Cancer Cells; IL-12 gene-transduction; MHC Antigen; Cytotoxic T-Lymphocytes(

The immunogenicity of human cancer cells is generally very low. Poorly immunogenic animal tumor cells can be converted into highly immunogenic tumors by several techniques. The purpose of this studies is to investigate whether UV-B-irradiated, IL-2 genetransduced, or IL-12 genetransduced human cancer cells are more immunogenic than untreated tunor cells with respect to MHC antigen expression, and the ability of inducing cytotoxic T lymphocyte (CTL) activity. UV-B radiation respectively decreased or increased MHC class I expression of freshly isolated tumor cells or cultured tumor cells, and also decreased MHC class I expression of starved cultured tumor cells. It increased the ability of both freshly isolated and cultured tumor cells to induce CTL activity from PBMC against untreated autologous tumor cells. These results indicated that UV radiation increased the ability of tumor cells to induce CTL activity without a corresponding effect on MHC antigen expression. Human renal cell carc … More inoma (RCC) cells transduced with human IL-2 gene (RCC-IL-2) stimulated PBMC to demonstrate LAK activity, and also stimulated autologous TILs to proliferate and exhibit cytotoxicity relatively restricted to autologous tumor cells. In contrast, both parental RCC and RCC transduced with neomycin gene alone failed to induce these activities. These results indicate that RCC-IL-2 cells are more potent than the other RCC cells with regard to inducing cytotoxic lymphocytes against autologous tumor cells. IL-12 genetransduced squamous cell carcinoma (IL-12-SCC) cells displayd enhanced expression of MHC class I antigen to induce autologous CTL against autologous SCC cells more potently than parental, non-IL-12 gene-transduced SCC cells. The main effector cells that exhibited relatively specific cytolysis against parental SCC cells were CD16+CD56+cells. In addition IL-12 gene-SCC cells were more susceptible to those effector cells than parental SCC cells. These results suggest that IL-12 may be able to maintain NK-cells for a long -term to display major, specific cytotoxicity and IL-12-SCC cells are well-recognized to lyse by those effector cells. In summary, UV radiation, IL-2, or IL-12 gene-transduction are potent methods to change tumor cells to induce CTL,or activated NK-cells with or without a corresponding effects on MHC antigen expression. Less

人类癌细胞的免疫原性通常很低。免疫原性差的动物肿瘤细胞可以通过几种技术转化为免疫原性高的肿瘤。本研究的目的是研究经UV-B照射、IL-2基因转导或IL-12基因转导的人癌细胞是否比未经处理的肿瘤细胞在MHC抗原表达和诱导细胞毒性T淋巴细胞（CTL）活性方面具有更强的免疫原性。UV-B辐射分别降低或增加新鲜分离的肿瘤细胞或培养的肿瘤细胞的MHC I类表达，并且还降低饥饿培养的肿瘤细胞的MHC I类表达。它增加了新鲜分离和培养的肿瘤细胞诱导PBMC对未处理的自体肿瘤细胞的CTL活性的能力。这些结果表明，紫外线辐射增强了肿瘤细胞诱导CTL活性的能力，而对MHC抗原表达没有相应的影响。人肾细胞癌 ...更多信息 用人IL-2基因转导的肾细胞瘤（RCC）细胞（RCC-IL-2）刺激PBMC以显示LAK活性，并且还刺激自体TIL增殖并显示相对限于自体肿瘤细胞的细胞毒性。与此相反，亲本RCC和单独转导新霉素基因的RCC均不能诱导这些活性。这些结果表明，RCC-IL-2细胞在诱导针对自体肿瘤细胞的细胞毒性淋巴细胞方面比其他RCC细胞更有效。IL-12基因转导的鳞状细胞癌（SCC）细胞比未转导IL-12基因的SCC细胞表现出更强的MHC I类抗原表达，从而更有效地诱导针对自体SCC细胞的自体CTL。对亲本SCC细胞表现出相对特异性细胞溶解的主要效应细胞是CD 16 + CD 56+细胞。此外，IL-12基因-SCC细胞比亲本SCC细胞更易受这些效应细胞的影响。这些结果表明，IL-12可能能够长期维持NK细胞以显示主要的特异性细胞毒性，并且IL-12-SCC细胞被这些效应细胞充分识别为裂解。总之，UV辐射、IL-2或IL-12基因转导是改变肿瘤细胞以诱导CTL或活化NK细胞的有效方法，其对MHC抗原表达具有或不具有相应的影响。少

项目成果

Kyogi ITOH: "Increase capability of Interleukin 2gene-Transduced Renal Cell earcinoms cells induce cytotoxic Lymphocytes21GC01:The Kurume Medical Journal" 41. 53-63 (1994)

Kyogi ITOH：“增加白细胞介素 2 基因转导的肾细胞癌细胞诱导细胞毒性淋巴细胞的能力21GC01：久留米医学杂志”41. 53-63 (1994)

Yasuiki Umezu: "Characterization of IL-12 induced effector cells and augmentaton of Susceptibility of tumor cells to effector cells by IL-12gene-Transduction" Cancer Res. (発表予定).

Yasuiki Umezu：“IL-12 诱导效应细胞的表征以及通过 IL-12 基因转导增强肿瘤细胞对效应细胞的敏感性”Cancer Res。

Yasuiki Umezu.: "Increase in the ability of human cancer cells toinduce cytotoxic T Lymphocytes by ultravidet irradiation." Cancer Immunology Immunotherapy. 37. 392-399 (1993)

Yasuiki Umezu.：“通过紫外线照射增强人类癌细胞诱导细胞毒性 T 淋巴细胞的能力。”

Yasuiki Umezu: "Characteri zation f IL-12 induced effector cells and augmentation of susceptibility of tumor cells to effector cells by IL-12 gene-transduction." in preparation for Cancer Res.

Yasuiki Umezu：“IL-12 诱导效应细胞的表征以及通过 IL-12 基因转导增强肿瘤细胞对效应细胞的敏感性。”

Kyogo Itoh: "Increase in the Capabitity of Interleukin 2 Gene-Transduced Kanal Cell Carcinoma Cells to induce Cytotoxic Lymphocytes." The KURUME MEDICAL JOURNAL. Vol41. 53-63 (1994)

Kyogo Itoh：“增加白细胞介素 2 基因转导的 Kanal 细胞癌细胞诱导细胞毒性淋巴细胞的能力。”