Cui Zhengrong, Qiu Fu
Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, OR 97331, USA.
Cancer Immunol Immunother. 2006 Oct;55(10):1267-79. doi: 10.1007/s00262-005-0114-6. Epub 2005 Dec 16.
Due to the inherent lack of immunogenicity of peptides, it is generally recognized that the strong inflammatory signals that are required to elicit specific responses against peptide-based therapeutic tumor vaccines may not be provided by the standard/conventional vaccine adjuvants. In this study, we have demonstrated dsRNA in the form of synthetic pI:C as a potent adjuvant to enhance the specific anti-tumor immune responses against a peptide-based vaccine. When complexed with an MHC I-restricted minimal peptide epitope derived from the HPV 16 E7 protein, the resulting pI:C/E7(49-57) molecular complex induced strong E7(49-57)-specific CTL responses that caused significant regressions of model human cervical cancer tumors pre-established in mice. In addition, although the proportion of DCs in tumor-bearing mice was significantly decreased when compared to that in naïve mice, immunization with pI:C/E7(49-57 )restored the proportion of DCs in tumor-bearing mice. Double-stranded RNA may hold a great potential as an adjuvant to induce cellular immune responses for tumor immunotherapy.
由于肽固有的免疫原性不足,人们普遍认为标准/传统疫苗佐剂可能无法提供引发针对基于肽的治疗性肿瘤疫苗的特异性反应所需的强烈炎症信号。在本研究中,我们已证明合成的聚肌苷酸-聚胞苷酸(pI:C)形式的双链RNA(dsRNA)作为一种有效的佐剂,可增强针对基于肽的疫苗的特异性抗肿瘤免疫反应。当与源自人乳头瘤病毒16 E7蛋白的MHC I类限制性最小肽表位复合时,所得的pI:C/E7(49-57)分子复合物诱导强烈的E7(49-57)特异性CTL反应,导致预先在小鼠中建立的人宫颈癌模型肿瘤显著消退。此外,尽管与未感染小鼠相比,荷瘤小鼠中树突状细胞(DC)的比例显著降低,但用pI:C/E7(49-57)免疫可恢复荷瘤小鼠中DC的比例。双链RNA作为诱导肿瘤免疫治疗细胞免疫反应的佐剂可能具有巨大潜力。