Department of Pathogenic Biology and Immunology, Medical School, Southeast University, Nanjing, China.
Scand J Immunol. 2013 Jul;78(1):69-78. doi: 10.1111/sji.12074.
In this study, we hypothesized that the mice immunized with the glycosylphosphatidylinositol (GPI) anchored 6-kDa early-secreted antigenic target (ESAT-6) DNA vaccine (ESAT-6-gpi) and the tumour vaccine B16F10-ESAT-6-gpi/IL-21 might significantly enhance immune responses and antimelanoma efficacy. Our experimental results indicated that the anti-ESAT-6 antibody induced by the DNA vaccine ESAT-6-gpi bound ESAT-6 to the surface of tumour vaccine to activate a complement classical pathway and resulted in the B16F10 tumour cell lysis and apoptosis, which served as a potential trigger for breaking melanomatous immune tolerance to elicit an initiation of natural antimelanoma immunity. Our innovative approach of using the DNA vaccine ESAT-6-gpi priming and the tumour vaccine B16F10-ESAT-6-gpi/IL-21 boosting induced strong antimelanoma immunity that inhibited melanomatous growth. These findings highlighted the DNA vaccine ESAT-6-gpi as an immune enhancer to augment the immune efficacy of the tumour vaccine B16F10-ESAT -6-gpi/IL-21 against melanoma in a mouse model.
在这项研究中，我们假设用糖基磷脂酰肌醇（GPI）锚定的 6kDa 早期分泌抗原靶（ESAT-6）DNA 疫苗（ESAT-6-gpi）和肿瘤疫苗 B16F10-ESAT-6-gpi/IL-21 免疫的小鼠会显著增强免疫反应和抗黑色素瘤功效。我们的实验结果表明，DNA 疫苗 ESAT-6-gpi 诱导的抗 ESAT-6 抗体与肿瘤疫苗上的 ESAT-6 结合，激活补体经典途径，导致 B16F10 肿瘤细胞裂解和凋亡，这可能是打破黑色素瘤免疫耐受的潜在触发因素，引发天然抗黑色素瘤免疫的启动。我们使用 DNA 疫苗 ESAT-6-gpi 进行初始免疫和肿瘤疫苗 B16F10-ESAT-6-gpi/IL-21 进行加强免疫的创新方法，诱导了强烈的抗黑色素瘤免疫，抑制了黑色素瘤的生长。这些发现强调了 DNA 疫苗 ESAT-6-gpi 作为免疫增强剂，可增强肿瘤疫苗 B16F10-ESAT-6-gpi/IL-21 在小鼠模型中对黑色素瘤的免疫疗效。
