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目的:为取得较佳的肿瘤免疫而伴随较小的自免疫损伤的途径,比较了接种腺病毒载体(Ad)介导人黑色素瘤相关抗原酪氨酸酶相关蛋白2(Trp2)时的不同途径与其效果的关系。方法:使用Ad编码的人Trp2(Ad hTrp2)分别不同途径(皮内id、肌注im和静脉注射iv)注射免疫C57BL/6小鼠(分为id组i、m组和iv组),每组给予不同免疫剂量(105,106,107,108,每组剂量10只小鼠),2周后,用体内细胞毒性T淋巴细胞(CTL)杀伤试验分析CTL杀伤活性及其量效关系。并于id和im时比较多次与单次的免疫效应,观察免疫2周鼠(每组剂量10只小鼠)皮下接种105B16F10黑色素瘤细胞后的肿瘤保护及白癜风形成情况,持续3个月。结果:(1)3种注射途径中,Ad hTrp2诱发小鼠CTL杀伤活性与其免疫剂量呈明确的量效关系,其中,im和id注射活性较iv强烈。(2)im和id注射时,重复与单次的疫苗免疫效果无明显差异。(3)Ad hTrp2免疫小鼠,其肿瘤保护作用于3个月的观察中持续存在。(4)而局部白癜风形成只在Ad hTrp2id组发现,于Ad hTrp2im未发现白癜风。这说明:Ad介导异种基因hTrp2的单次免疫即有效地克服了自身mTRP2的免疫耐受,诱发了强烈的抗原特异性细胞免疫反应。同时,通过im的免疫途径,诱发了较强的抗肿瘤免疫效果,可有效克服自身免疫损伤。结论:自身免疫损伤并不是一定伴随较强的抗肿瘤免疫而出现。
OBJECTIVE: To compare the different pathways in which adenovirus vector (Ad) mediated the human melanoma-associated antigen tyrosinase-related protein 2 (Trp2) in order to obtain better tumor immunity with less autoimmune damage Relationship with its effect. Methods: C57BL / 6 mice were randomly divided into id group (group i, group m and group iv) by different routes (intradermal id, intramuscular im and iv) using Ad-encoding human Trp2 Groups were given different doses (105, 106, 107, 108, 10 mice per group). Two weeks later, cytotoxic T lymphocyte (CTL) killing assay was used to analyze CTL killing activity and its dose-response relationship. And in the id and im more and more single immunization effect observed 2 weeks immunized mice (10 mice per group) subcutaneously inoculated with 105B16F10 melanoma cells after tumor protection and vitiligo formation for 3 months. Results: (1) Among the three injection routes, there was a clear dose-effect relationship between the immunosuppressive activity of CTL induced by Ad hTrp2 and the immunosuppressive effect of imhTrp2. Among them, the im and id injection activity was stronger than iv. (2) im and id injection, repeated and single vaccine effect no significant difference. (3) Ad hTrp2 immunized mice whose tumor protective effect persisted for 3 months. (4) The formation of local vitiligo was found only in Ad hTrp2id group, no vitiligo was found in Ad hTrp2im. This shows that Ad-mediated single immunization of the heterologous gene hTrp2 effectively overcomes the immune tolerance of its own mTRP2 and induces a strong antigen-specific cellular immune response. At the same time, through the im immune route, induced a strong anti-tumor immune effect, can effectively overcome the autoimmune damage. Conclusion: Autoimmune damage does not necessarily occur with strong anti-tumor immunity.