Lentivector immunization induces tumor antigen-specific B and T cell responses in vivo
Lentivector immunization induces tumor antigen-specific B and T cell responses in vivo
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DOI：
10.1002/eji.200737923
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发表时间：
2008-07-01
影响因子：
5.4
通讯作者：
Levy, Frederic
中科院分区：
文献类型：
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作者：
Casado, Javier Garcia;Janda, Jozef;Levy, Frederic
肿瘤细胞表达肿瘤/生殖系抗原NY-ESO-1可诱导某些肿瘤患者产生自发的体液和细胞免疫反应。开发能够刺激这种全面免疫反应的疫苗是可取的。我们制备了指导NY-ESO-1细胞内合成的重组慢病毒载体(RLV/ESO)，并分析了该载体诱导的体内免疫应答。单次注射RLV/ESO可诱导针对NY-ESO-1的长效B细胞和T细胞应答。抗HLAA2限制性多肽NY-ESO-1157-165的CD8(+)T细胞在体外很容易被检测到，并且表现出有限的TCR VP用途。此外，RLV/ESO诱导的抗NY-ESO-11-57-165CD8‘T细胞反应比基于多肽或蛋白质的疫苗强得多。免疫后迅速产生抗NY-ESO-1抗体，其检测先于抗原特异性CD8(+)T细胞。RLV/ESO还可诱导CD4(+)T细胞。这些细胞发挥了至关重要的作用，因为它们的耗尽完全消除了B细胞和CD8(+)T细胞对NY-ESO-1的反应。诱导的CD4(+)T细胞主要针对一个跨度为81-100个氨基酸的NY-ESO-1表位。综上所述，我们的研究表明RLV/ESO在体内诱导了强大而全面的免疫反应。
Expression of the cancer/germ-line antigen NY-ESO-1 by tumors elicits spontaneous humoral and cellular immune responses in some cancer patients. Development of vaccines capable of stimulating such comprehensive immune responses is desirable. We have produced recombinant lentivectors directing the intracellular synthesis of NY-ESO-1 (rLV/ ESO) and have analyzed the in vivo immune response elicited by this vector. Single injection of rLV/ESO into HLA-A2-transgenic mice elicited long-lasting B and T cell responses against NY-ESO-1. CD8(+) T cells against the HLA-A2-restricted peptide NY-ESO-1157-165 were readily detectable ex vivo and showed restricted TCR VP usage. Moreover, rLV/ESO elicited a far greater anti-NY-ESO-11-57-165 CD8' T cell response than peptide- or protein-based vaccines. Anti-NY-ESO-1 antibodies were rapidly induced after immunization and their detection preceded that of the antigen-specific CD8(+) T cells. The rLV/ESO also induced CD4(+) T cells. These cells played an essential role as their depletion completely abrogated B cell and CD8(+) T cell responses against NY-ESO-1. The induced CD4(+) T cells were primarily directed against a single NY-ESO-1 epitope spanning amino acids 81-100. Altogether, our study shows that rLV/ESO induces potent and comprehensive immune responses in vivo.