Ressing M E, van Driel W J, Celis E, Sette A, Brandt M P, Hartman M, Anholts J D, Schreuder G M, ter Harmsel W B, Fleuren G J, Trimbos B J, Kast W M, Melief C J
Department of Immunohematology, University Hospital Leiden, The Netherlands.
Cancer Res. 1996 Feb 1;56(3):582-8.
Most cervical carcinoma (Cxca) cells constitutively express human papillomavirus type 16 (HPV16) E6 and E7 oncoproteins. These proteins are, therefore, attractive targets for T cell-based immunotherapy. Previously, we identified HVP16 E7-encoded CTL epitopes. In patients with cervical intraepithelial neoplasia or Cxca, little is known concerning T-cell activity against viruses in general and against HPV16 in particular. Here, we have screened the blood of 10 healthy donor controls and of 22 patients with HPV16+ cervical lesions for the presence of CTLs directed against HPV16 E7- and control influenza virus matrix-derived epitopes presented by HLA-A *0201. We detected influenza virus-specific CTLs in all donors and in the majority of patients, indicating that most patients have functioning T-cell responses despite their lesions or therapeutic interventions. Moreover, we show that patients with HPV16+ lesions occasionally have memory CTLs against a HPV16 E7-encoded epitope (sequence YMLD-LQPETT), providing evidence for natural CTL immunity against HPV16 in patients with cervical lesions. Combined, these findings raise possibilities for vaccination with HPV16 E7-encoded peptides to induce or augment CTL responses for treatment or prevention of Cxca.
大多数宫颈癌（Cxca）细胞组成性表达人乳头瘤病毒16型（HPV16）E6和E7癌蛋白。因此，这些蛋白是基于T细胞免疫疗法的有吸引力的靶点。此前，我们鉴定了HPV16 E7编码的CTL表位。在宫颈上皮内瘤变或Cxca患者中，对于一般针对病毒尤其是针对HPV16的T细胞活性知之甚少。在此，我们筛查了10名健康供体对照和22名HPV16阳性宫颈病变患者的血液，以检测针对由HLA-A *0201呈递的HPV16 E7和对照流感病毒基质衍生表位的CTL的存在情况。我们在所有供体和大多数患者中检测到了流感病毒特异性CTL，这表明尽管患者有病变或接受了治疗干预，但大多数患者仍具有功能性T细胞反应。此外，我们表明HPV16阳性病变患者偶尔有针对HPV16 E7编码表位（序列YMLD-LQPETT）的记忆CTL，这为宫颈病变患者针对HPV16的天然CTL免疫提供了证据。综合来看，这些发现增加了用HPV16 E7编码肽进行疫苗接种以诱导或增强CTL反应来治疗或预防Cxca的可能性。
