Valmori Danila, Souleimanian Naira E, Tosello Valeria, Bhardwaj Nina, Adams Sylvia, O'Neill David, Pavlick Anna, Escalon Juliet B, Cruz Crystal M, Angiulli Angelica, Angiulli Francesca, Mears Gregory, Vogel Susan M, Pan Linda, Jungbluth Achim A, Hoffmann Eric W, Venhaus Ralph, Ritter Gerd, Old Lloyd J, Ayyoub Maha
Ludwig Institute Clinical Trial Center, Columbia University, New York, NY 10032, USA.
Proc Natl Acad Sci U S A. 2007 May 22;104(21):8947-52. doi: 10.1073/pnas.0703395104. Epub 2007 May 15.
The use of recombinant tumor antigen proteins is a realistic approach for the development of generic cancer vaccines, but the potential of this type of vaccines to induce specific CD8(+) T cell responses, through in vivo cross-priming, has remained unclear. In this article, we report that repeated vaccination of cancer patients with recombinant NY-ESO-1 protein, Montanide ISA-51, and CpG ODN 7909, a potent stimulator of B cells and T helper type 1 (Th1)-type immunity, resulted in the early induction of specific integrated CD4(+) Th cells and antibody responses in most vaccinated patients, followed by the development of later CD8(+) T cell responses in a fraction of them. The correlation between antibody and T cell responses, together with the ability of vaccine-induced antibodies to promote in vitro cross-presentation of NY-ESO-1 by dendritic cells to vaccine-induced CD8(+) T cells, indicated that elicitation of NY-ESO-1-specific CD8(+) T cell responses by cross-priming in vivo was associated with the induction of adequate levels of specific antibodies. Together, our data provide clear evidence of in vivo cross-priming of specific cytotoxic T lymphocytes by a recombinant tumor antigen vaccine, underline the importance of specific antibody induction for the cross-priming to occur, and support the use of this type of formulation for the further development of efficient cancer vaccines.
使用重组肿瘤抗原蛋白是开发通用型癌症疫苗的一种切实可行的方法，但是这类疫苗通过体内交叉致敏诱导特异性CD8(+) T细胞应答的潜力仍不明确。在本文中，我们报告称，用重组NY-ESO-1蛋白、Montanide ISA-51和CpG ODN 7909（一种B细胞和1型辅助性T细胞（Th1）免疫的强效刺激剂）反复接种癌症患者，在大多数接种患者中导致了特异性整合CD4(+) Th细胞和抗体应答的早期诱导，随后部分患者出现了后期CD8(+) T细胞应答。抗体与T细胞应答之间的相关性，以及疫苗诱导的抗体促进树突状细胞将NY-ESO-1体外交叉呈递给疫苗诱导的CD8(+) T细胞的能力，表明体内通过交叉致敏诱导NY-ESO-1特异性CD8(+) T细胞应答与诱导足够水平的特异性抗体有关。总之，我们的数据为重组肿瘤抗原疫苗在体内交叉致敏特异性细胞毒性T淋巴细胞提供了明确证据，强调了诱导特异性抗体对交叉致敏发生的重要性，并支持使用这种制剂进一步开发高效癌症疫苗。
