De Bruijn M L, Schuurhuis D H, Vierboom M P, Vermeulen H, de Cock K A, Ooms M E, Ressing M E, Toebes M, Franken K L, Drijfhout J W, Ottenhoff T H, Offringa R, Melief C J
Department of Immunohematology and Blood Bank, University Hospital Leiden, The Netherlands.
Cancer Res. 1998 Feb 15;58(4):724-31.
Human papillomavirus (HPV) E6 and E7 oncoproteins are attractive targets for T-cell-based immunotherapy of cervical cancer. In this study, we demonstrate that dendritic cells (DCs) pulsed with HPV16 E7 protein are not only recognized in vitro by E7-specific CTLs but also elicit E7-specific CTL responses in vivo, associated with protection against a challenge with syngeneic HPV16-induced tumor cells. Vaccination with soluble E7 protein in incomplete Freund's adjuvant likewise induces E7-specific CTL responses associated with tumor protection. The presence of HPV16 E7-specific CTLs in vivo and the observation that depletion of CD8+ cells completely abolishes tumor protection demonstrate that CTLs are the major effector cells in mediating antitumor activity. The in vivo involvement of DCs in the activation of protective CTLs is suggested by the surface display of E7 peptide-loaded MHC class I molecules on these cells after E7 protein immunization. These data show that HPV16 E7 protein-pulsed DCs, as well as the administration of E7 protein antigen in adjuvant, can effectively stimulate tumor-specific MHC class I-restricted CD8+ T-cell-mediated protective immunity to HPV16-induced cancers.
人乳头瘤病毒（HPV）E6和E7癌蛋白是基于T细胞的宫颈癌免疫疗法的理想靶点。在本研究中，我们证明用HPV16 E7蛋白脉冲处理的树突状细胞（DC）不仅在体外被E7特异性CTL识别，而且在体内引发E7特异性CTL反应，这与针对同基因HPV16诱导的肿瘤细胞攻击的保护作用相关。用不完全弗氏佐剂中的可溶性E7蛋白进行疫苗接种同样诱导与肿瘤保护相关的E7特异性CTL反应。体内存在HPV16 E7特异性CTL以及CD8 +细胞耗竭完全消除肿瘤保护作用的观察结果表明，CTL是介导抗肿瘤活性的主要效应细胞。E7蛋白免疫后这些细胞上E7肽负载的MHC I类分子的表面展示提示了DC在体内参与保护性CTL的激活。这些数据表明，HPV16 E7蛋白脉冲处理的DC以及佐剂中E7蛋白抗原的给药可以有效地刺激针对HPV16诱导的癌症的肿瘤特异性MHC I类限制性CD8 + T细胞介导的保护性免疫。
