Cornet Sébastien, Miconnet Isabelle, Menez Jeanne, Lemonnier François, Kosmatopoulos Kostas
Vaxon Biotech, Génopole bat G2, 2 rue Gaston Crémieux, 91057 Evry, France.
Vaccine. 2006 Mar 15;24(12):2102-9. doi: 10.1016/j.vaccine.2005.11.015. Epub 2005 Nov 28.
Polyspecific tumor vaccination should offer broad control of tumor cells and reduce the risk of emergence of immune escape variants. Here, we evaluated the capacity of a polypeptide composed of optimized cryptic peptides derived from three different universal tumor antigens (TERT988Y, HER-2/neu402Y and MAGE-A248V9) to induce a polyspecific CD8 cell response both in vivo in HHD mice and in vitro in humans. A mixture of TERT988Y, HER-2/neu402Y and MAGE-A248V9 peptides failed to induce a trispecific response. In contrast, a polypeptide composed of the three peptides stimulated a trispecific immune response. Interestingly, the capacity of the polypeptide to induce a trispecific response depended on its internal organization. Six different polypeptide variants corresponding to all possible combinations of the three peptides were tested. Only one variant, named Poly-6, elicited an immune response simultaneously targeting all three peptides.
多特异性肿瘤疫苗接种应能广泛控制肿瘤细胞，并降低免疫逃逸变体出现的风险。在此，我们评估了一种由源自三种不同通用肿瘤抗原（TERT988Y、HER-2/neu402Y和MAGE-A248V9）的优化隐蔽肽组成的多肽在HHD小鼠体内和人体体外诱导多特异性CD8细胞反应的能力。TERT988Y、HER-2/neu402Y和MAGE-A248V9肽的混合物未能诱导三特异性反应。相比之下，由这三种肽组成的多肽刺激了三特异性免疫反应。有趣的是，该多肽诱导三特异性反应的能力取决于其内部结构。测试了与这三种肽的所有可能组合相对应的六种不同多肽变体。只有一种名为Poly-6的变体引发了同时靶向所有三种肽的免疫反应。
