Superior induction of anti-tumor CTL immunity by extended peptide vaccines involves prolonged, DC-focused antigen presentation
Superior induction of anti-tumor CTL immunity by extended peptide vaccines involves prolonged, DC-focused antigen presentation
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DOI：
10.1002/eji.200737995
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发表时间：
2008-04-01
影响因子：
5.4
通讯作者：
Offringa, Rienk
中科院分区：
文献类型：
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作者：
Bijker, Martijn S.;van den Eeden, Susan J. E.;Offringa, Rienk
由延伸的CTL肽与CpG-ODN组合组成的抗肿瘤疫苗显示出上级于包含最小CTL表位和CpG-ODN的那些疫苗，因为它们引发具有更大杀肿瘤潜力的更强效应CTL应答。我们现在证明，这种改善的性能主要是由于CTL表位呈递集中在引流疫苗接种部位的发炎淋巴结中的活化DC上。在用最小肽接种的情况下，包括T和B细胞的另外的APC也负载有CTL表位。我们的数据表明，这些肽负载的淋巴细胞的循环导致表位呈递在非发炎的淋巴器官远离接种部位，在有效的CTL引发所需的有效的共刺激信号的情况下。通过用延伸的CTL肽接种避免了导致CTL应答的次优活化的原免疫原性和致耐受性信号的所得混合物。延长的CTL肽疫苗的另一个优点是体内表位呈递的持续时间增加。
Anti-tumor vaccines consisting of extended CTL peptides in combination with CpG-ODN were shown to be superior to those comprising minimal CTL epitopes and CpG-ODN, in that they elicit stronger effector CTL responses with greater tumoricidal potential. We now demonstrate that this improved performance is primarily due to the focusing of CTL epitope presentation onto activated DC in the inflamed lymph nodes draining the vaccination site. In the case of vaccination with minimal peptides, additional APC including T and B cells are also loaded with CTL epitopes. Our data suggest that circulation of these peptide-loaded lymphocytes leads to epitope presentation in non-inflamed lymphoid organs distal from the vaccination site, in the absence of potent costimulatory signals required for efficient CTL priming. The resulting blend of pro-immunogenic and tolerogenic signals, which results in suboptimal activation of the CTL response, is avoided by vaccinating with extended CTL peptides. An additional advantage of extended CTL peptide vaccines is an increased duration of in vivo epitope presentation.