Zagury D, Le Buanec H, Bizzini B, Burny A, Lewis G, Gallo R C
Université Pierre et Marie Curie, 15 rue de l'Ecole de Médecine, 75006, Paris, France.
Cytokine Growth Factor Rev. 2003 Apr;14(2):123-37. doi: 10.1016/s1359-6101(03)00004-2.
Current therapeutic vaccine trials in major chronic diseases including AIDS, cancer, allergy and autoimmunity, target antigenic pathogens but not the pathogenic stromal cytokines which can be major sources of histopathologic processes. Considering that the limited efficacy of these vaccines has been ascribed to local pathogen-induced cytokine dysfunction, we propose to antagonize pathogenic cytokine(s) by high affinity neutralizing auto-Abs triggered by specific anti-cytokine vaccines. As anticipated by theoretical considerations, animal experiments and initial clinical trials showed that anti-cytokine immunization was safe, well tolerated and triggered transient high titers Abs neutralizing pathogenic cytokines but, in contrast to conventional vaccines, no relevant cellular response was observed. Advantages of active versus passive anti-cytokine Ab therapy, particularly for long-term treatments, as those required in AIDS, cancer, allergy and autoimmunity include greater ease of maintaining high Ab titers, lack of anti-antibody responses and low cost.
目前针对包括艾滋病、癌症、过敏和自身免疫性疾病在内的主要慢性疾病进行的治疗性疫苗试验，其目标是抗原性病原体，而非致病的基质细胞因子，而这些细胞因子可能是组织病理学过程的主要来源。鉴于这些疫苗的疗效有限归因于局部病原体诱导的细胞因子功能障碍，我们建议通过由特定抗细胞因子疫苗触发的高亲和力中和自身抗体来拮抗致病细胞因子。正如理论考量、动物实验和初步临床试验所预期的那样，抗细胞因子免疫接种是安全的，耐受性良好，并能触发中和致病细胞因子的短暂高滴度抗体，但与传统疫苗不同的是，未观察到相关的细胞反应。主动抗细胞因子抗体疗法与被动抗细胞因子抗体疗法相比，特别是对于艾滋病、癌症、过敏和自身免疫性疾病所需的长期治疗而言，具有更易于维持高抗体滴度、缺乏抗抗体反应以及成本低等优势。
