Paul Stéphane, Acres Bruce, Limacher Jean-Marc, Bonnefoy Jean-Yves
Transgene SA, Research and Development, 11 rue de Molsheim, 67082 Strasbourg, France.
IDrugs. 2007 May;10(5):324-8.
Therapeutic vaccination against cancer-associated antigens represents an attractive option for cancer therapy in view of its efficacy, the possibility of long-lasting immunity against the cancer, and safety profile. Nevertheless, it is now recognized that the same vaccination strategies used for prophylactic vaccinations against infectious diseases, cannot necessarily be used for therapeutic cancer vaccination. Cancer patients are usually immunosuppressed and most cancer-associated antigens are 'self-antigens', making it a significant challenge to vaccinate patients against a cancer-associated antigen. Various immunostimulation techniques are under investigation in an effort to bolster patients' immune systems and to overcome immune tolerance to self antigens. Strategies to stimulate antigen presentation, T-cell reactivity and innate immune activity are under investigation. Several clinical trials have been conducted to evaluate therapeutic cancer vaccines in patients, and attractive protocols, including those that combine the stimulation of specific T-cells and chemotherapy, or strategies to block immune regulation, are beginning to show some success. This feature review considers strategies for the development of effective therapeutic cancer vaccines, and highlights select vaccines that have already entered the clinic.
鉴于其疗效、对癌症产生持久免疫力的可能性以及安全性,针对癌症相关抗原的治疗性疫苗接种是癌症治疗的一个有吸引力的选择。然而,现在人们认识到,用于预防传染病的相同疫苗接种策略不一定能用于治疗性癌症疫苗接种。癌症患者通常免疫功能低下,而且大多数癌症相关抗原是“自身抗原”,这使得给患者接种针对癌症相关抗原的疫苗成为一项重大挑战。各种免疫刺激技术正在研究中,以增强患者的免疫系统并克服对自身抗原的免疫耐受。刺激抗原呈递、T细胞反应性和先天免疫活性的策略正在研究中。已经进行了几项临床试验来评估患者的治疗性癌症疫苗,包括那些将特异性T细胞刺激与化疗相结合的方案,或阻断免疫调节的策略,这些有吸引力的方案开始显示出一些成功迹象。这篇专题综述探讨了开发有效的治疗性癌症疫苗的策略,并重点介绍了一些已经进入临床试验阶段的疫苗。