Development of tumor immunotherapy by vaccinated cancer cells

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高免疫原性肿瘤。本研究的目的是探讨uv - b照射、IL-2基因转导或IL-12基因转导的人癌细胞在MHC抗原表达和诱导细胞毒性T淋巴细胞（CTL）活性方面是否比未处理的肿瘤细胞更具免疫原性。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MHC I类表达，也降低饥饿培养的肿瘤细胞MHC I类表达。它增加了新分离和培养的肿瘤细胞诱导PBMC对未经处理的自体肿瘤细胞的CTL活性的能力。这些结果表明，紫外线辐射增加了肿瘤细胞诱导CTL活性的能力，但对MHC抗原的表达没有相应的影响。转染人IL-2基因（RCC-IL-2）的瘤细胞（RCC）刺激PBMC显示LAK活性，同时也刺激自体TILs增殖并表现出相对局限于自体肿瘤细胞的细胞毒性。相比之下，亲本RCC和单独用新霉素基因转导的RCC都不能诱导这些活性。这些结果表明，RCC- il -2细胞在诱导细胞毒性淋巴细胞对抗自体肿瘤细胞方面比其他RCC细胞更有效。IL-12基因转导的鳞状细胞癌（IL-12-SCC）细胞比亲代非IL-12基因转导的SCC细胞更能增强MHC I类抗原的表达，诱导自体CTL对抗自体SCC细胞。对亲代SCC细胞表现出相对特异性细胞溶解的主要效应细胞是CD16+CD56+细胞。此外，IL-12基因SCC细胞比亲本SCC细胞更容易受到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细胞表现出主要的、特异性的细胞毒性，并且IL-12- scc细胞被这些效应细胞很好地识别为裂解。总之，紫外线辐射、IL-2或IL-12基因转导是改变肿瘤细胞诱导CTL或活化nk细胞的有效方法，对MHC抗原表达有或没有相应的影响。少

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