Disis M L, Schiffman K
Division of Oncology, University of Washington, Seattle, WA 98195-6527, USA.
Semin Oncol. 2001 Dec;28(6 Suppl 18):12-20.
Several advances in basic immunology over the last few years have forced a re-evaluation of cancer vaccine development. The most important finding has been that human tumors are immunogenic. The HER2/neu oncogenic protein is a tumor antigen. Existent antibody, helper T-cell, and cytotoxic T-cell immunity to HER2/neu have been detected in patients with cancer. The HER2/neu protein is an excellent therapeutic target for the immune system. Passive immunotherapy strategies, such as the infusion of monoclonal antibodies specific for HER2/neu, have been shown to be of clinical benefit in patients with HER2/neu-overexpressing malignancies. Inducing an active immune response by generating endogenous HER2/neu-specific antibodies and T cells may result in long-lived immunity and, hopefully, therapeutic benefit. In the majority of patients with pre-existent HER2/neu immunity, the antigen-specific antibodies and T cells detected are of low magnitude. Therefore, vaccine strategies aimed at boosting immunity already present may be effective in generating significant levels of HER2/neu-specific antibodies and T cells.
过去几年基础免疫学的几项进展促使人们重新评估癌症疫苗的研发。最重要的发现是人类肿瘤具有免疫原性。HER2/neu致癌蛋白是一种肿瘤抗原。在癌症患者中已检测到针对HER2/neu的现有抗体、辅助性T细胞和细胞毒性T细胞免疫。HER2/neu蛋白是免疫系统极好的治疗靶点。被动免疫治疗策略,如输注针对HER2/neu的单克隆抗体,已被证明对HER2/neu过表达恶性肿瘤患者具有临床益处。通过产生内源性HER2/neu特异性抗体和T细胞诱导主动免疫反应可能会产生持久的免疫力,并有望带来治疗益处。在大多数已有HER2/neu免疫的患者中,检测到的抗原特异性抗体和T细胞水平较低。因此,旨在增强已有免疫力的疫苗策略可能有效地产生高水平的HER2/neu特异性抗体和T细胞。