Sullivan J B
Med Toxicol. 1986 Jan-Feb;1(1):47-60. doi: 10.1007/BF03259827.
Immunotherapy for reversal of toxicity due to poisons and drugs is not new. However, refinements in antibody isolation and purification as well as the advancement of hybridoma technology and recombinant DNA biotechnology has led to a new generation of immunotherapeutic and diagnostic agents. The advent of monoclonal antibody technology in 1975 heralded the new age of immunopharmacology and immunotoxicology. Monoclonal antibodies designed for a specific antigen resolved the problem of polyclonality and cross-reactivity of traditional antibodies. Along with the production and isolation of active antibody fragments from both polyclonal and human monoclonal sources, as well as the ability to tailor-make chimeric antibodies by recombinant biotechnology, the development of novel immunotherapeutic agents has taken place. Two immunotherapeutic modalities, digoxin-specific antibody fragments (Fab) and snake antivenin, have been available for the clinician's armamentarium for years. Along the same lines of anti-digoxin Fab development, application of newer antibody isolation technology has led to a purified IgG(T) antibody for snake venom poisoning which is still in the developmental stages. Potential future developments in immunotherapeutics must overcome the clinical problems of immunogenicity and adverse reactions to the antibodies. Human monoclonal sources, active antibody fragments, and chimeric antibodies from transfectomas are all potential resolutions to these problems.
用于逆转毒物和药物所致毒性的免疫疗法并非新鲜事物。然而,抗体分离与纯化技术的改进以及杂交瘤技术和重组DNA生物技术的发展,催生了新一代免疫治疗和诊断药物。1975年单克隆抗体技术的出现开创了免疫药理学和免疫毒理学的新时代。针对特定抗原设计的单克隆抗体解决了传统抗体的多克隆性和交叉反应问题。随着从多克隆和人单克隆来源生产和分离活性抗体片段,以及通过重组生物技术定制嵌合抗体能力的出现,新型免疫治疗药物得以开发。两种免疫治疗方式,即地高辛特异性抗体片段(Fab)和抗蛇毒血清,多年来一直是临床医生的可用武器。沿着抗地高辛Fab的研发路线,更新的抗体分离技术的应用已产生一种用于蛇毒中毒的纯化IgG(T)抗体,该抗体仍处于研发阶段。免疫治疗未来潜在的发展必须克服抗体的免疫原性和不良反应等临床问题。人单克隆来源、活性抗体片段以及转染瘤产生的嵌合抗体都是解决这些问题的潜在方法。