Texas A&M University, College of Veterinary Medicine and Biomedical Sciences, Texas A&M Health Science Center, Comparative Immunogenetics Laboratory, Department of Veterinary Pathobiology , Mailstop 4467, College Station, TX 77843 , USA +1 979 845 4207 ; +1 979 862 1088 ;
Expert Opin Drug Discov. 2014 Jul;9(7):725-39. doi: 10.1517/17460441.2014.920818. Epub 2014 May 16.
Sharks have successfully lived in marine ecosystems, often atop food chains as apex predators, for nearly one and a half billion years. Throughout this period they have benefitted from an immune system with the same fundamental components found in terrestrial vertebrates like man. Additionally, sharks have some rather extraordinary immune mechanisms which mammals lack.
In this review the author briefly orients the reader to sharks, their adaptive immunity, and their important phylogenetic position in comparative immunology. The author also differentiates some of the myths from facts concerning these animals, their cartilage, and cancer. From thereon, the author explores some of the more remarkable capabilities and products of shark lymphocytes. Sharks have an isotype of light chain-less antibodies that are useful tools in molecular biology and are moving towards translational use in the clinic. These special antibodies are just one of the several tricks of shark lymphocyte antigen receptor systems.
While shark cartilage has not helped oncology patients, shark immunoglobulins and T cell receptors do offer exciting novel possibilities for immunotherapeutics. Much of the clinical immunology developmental pipeline has turned from traditional vaccines to passively delivered monoclonal antibody-based drugs for targeted depletion, activation, blocking and immunomodulation. The immunogenetic tools of shark lymphocytes, battle-tested since the dawn of our adaptive immune system, are well poised to expand the design landscape for the next generation of immunotherapy products.
鲨鱼在海洋生态系统中成功生存了近 15 亿年，通常处于食物链的顶端，是顶级掠食者。在此期间，它们受益于与人类等陆地脊椎动物相同的基本组成部分的免疫系统。此外，鲨鱼还有一些哺乳动物所缺乏的相当非凡的免疫机制。
在这篇综述中，作者简要地引导读者了解鲨鱼、它们的适应性免疫系统，以及它们在比较免疫学中的重要进化地位。作者还区分了一些关于这些动物、它们的软骨和癌症的神话和事实。此后，作者探讨了鲨鱼淋巴细胞的一些更显著的能力和产物。鲨鱼有一种无轻链的抗体同工型，它是分子生物学中的有用工具，并正在向临床转化应用方向发展。这些特殊的抗体只是鲨鱼淋巴细胞抗原受体系统的几个技巧之一。
虽然鲨鱼软骨对肿瘤患者没有帮助，但鲨鱼免疫球蛋白和 T 细胞受体确实为免疫治疗提供了令人兴奋的新可能性。许多临床免疫学的发展管道已经从传统疫苗转向被动传递基于单克隆抗体的药物，用于靶向耗竭、激活、阻断和免疫调节。鲨鱼淋巴细胞的免疫遗传学工具，自我们的适应性免疫系统出现以来就经过了考验，它们很有可能为下一代免疫治疗产品的设计提供更多的可能性。
