Relevance of the tumor antigen in the validation of three vaccination strategies for melanoma
Relevance of the tumor antigen in the validation of three vaccination strategies for melanoma
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DOI：
10.4049/jimmunol.165.5.2651
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发表时间：
2000-09-01
影响因子：
4.4
通讯作者：
Dellabona, P
中科院分区：
文献类型：
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作者：
Bellone, M;Cantarella, D;Dellabona, P
许多癌症免疫治疗的临床前研究是基于在几种肿瘤模型中测试单一疫苗接种策略。此外，这些研究中的大多数使用异种Ag，由于其高免疫原性，其可能不代表用于验证癌症免疫疗法的现实模型。为了解决这些问题，我们比较了三种完善的策略（即，裸DNA;肽脉冲的树突状细胞（DC），或肽和大肠杆菌毒素LTR 72的混合物），在B16黑素瘤模型中使用异种OVA或天然表达的酪氨酸酶相关蛋白2（TRP-2）肿瘤Ag。C57 BL/6小鼠接受1至3次s.c.注射肽脉冲的DC或DNA，或1至4次粘膜施用肽-毒素混合物。1至2周后，动物皮下注射激发。用B16或表达OVA的B16细胞（B16-OVA）接种，在所有情况下用OVA接种小鼠诱导黑素瘤特异性CTL和针对B16-OVA的保护。当使用TRP-2时，所有三种疫苗都引发B16特异性CTL，但只有用免疫显性T细胞表位TRP-2（181-188）脉冲的DC允许针对B16的保护。甚至更重要的是，在注射致死数量的B16细胞后24小时开始的TRP-2脉冲DC的疫苗接种方案在60%的受攻击动物中引起治疗效果。我们的研究结果强烈强调了肿瘤抗原在癌症免疫策略定义中的相关性，并支持将肽脉冲DC用作人类癌症疫苗。
Many preclinical studies of cancer immunotherapy are based on the testing of a single vaccination strategy in several tumor models. Moreover, most of those studies used xenogeneic Ags, which, owing to their high immunogenicity, may not represent realistic models for the validation of cancer immunotherapies, To address these issues, we compared the vaccination efficacy of three well established strategies (i.e., naked DNA; peptide-pulsed dendritic cells (DC), or a mixture of peptide and the Escherichia coli toxin LTR72) using the xenogeneic OVA or the naturally expressed tyrosinase-related protein 2 (TRP-2) tumor Ag in the B16 melanoma model. C57BL/6 mice received one to three s.c. injections of peptide-pulsed DC or DNA, or one to four mucosal administrations of peptide-toxin mixture. One to 2 wk later, the animals were challenged s.c. with B16 or B16 cells expressing OVA (B16-OVA), Vaccination of mice with OVA induced in all cases melanoma-specific CTL and protection against B16-OVA, When TRP-2, was used, all three vaccines elicited B16-specific CTL, but only DC pulsed with the immunodominant T cell epitope TRP-2(181-188) allowed protection against B16. Even more importantly, a vaccination regimen with TRP-2-pulsed DC, started 24 h after the injection of a lethal number of B16 cells, caused a therapeutic effect in 60% of the challenged animals. Our results strongly emphasize the relevance of the tumor Ag in the definition of immunotherapeutic strategies for cancer, and support the use of peptide-pulsed DC as cancer vaccine in humans.