Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, the Netherlands.
Cancer J. 2011 Sep-Oct;17(5):300-1. doi: 10.1097/PPO.0b013e318235e0fe.
Until recently, therapeutic cancer vaccines only sporadically led to long-term clinical responses. We here report on a novel vaccine modality, characterized by the administration of long (23-45 amino acids) synthetic peptides in incomplete Freund adjuvant (mineral oil-based, Montanide ISA-51), delivered subcutaneously. Such vaccines were first demonstrated to be much more potent in preclinical T-cell response induction and tumor therapy experiments than short major histocompatibility complex class I-binding peptides that have been used extensively in the clinic. A long-peptide vaccine consisting of 13 overlapping peptides, together covering the entire length of the 2 oncogenic proteins E6 and E7 of high-risk human papilloma virus type 16 (HPV16), caused complete regression of all lesions and eradication of virus in 9 of 20 women with high-grade vulvar intraepithelial neoplasia. The nature and strength of the vaccine-induced T-cell response were significantly correlated with the clinical response. This vaccine promises to be of use, not only in patients with premalignant lesions caused by high-risk HPV16, but also in patients with malignant tumors caused by this virus, including HPV16-positive cervical cancer, anal cancer, and head and neck cancer.
直到最近,治疗性癌症疫苗才偶尔导致长期临床反应。我们在这里报告一种新的疫苗模式,其特征是在不完全弗氏佐剂(矿物油基,Montanide ISA-51)中给予长(23-45 个氨基酸)合成肽。与在临床上广泛使用的短主要组织相容性复合体 I 类结合肽相比,这种疫苗在临床前 T 细胞反应诱导和肿瘤治疗实验中被证明更有效。一种由 13 个重叠肽组成的长肽疫苗,共同覆盖高危型人乳头瘤病毒 16(HPV16)的 2 种致癌蛋白 E6 和 E7 的全长,导致 20 名高级别外阴上皮内瘤变女性中的 9 名完全消退所有病变并消除病毒。疫苗诱导的 T 细胞反应的性质和强度与临床反应显著相关。这种疫苗不仅有望用于高危 HPV16 引起的癌前病变患者,也有望用于该病毒引起的恶性肿瘤患者,包括 HPV16 阳性宫颈癌、肛门癌和头颈部癌。