What the shark immune system can and cannot provide for the expanding design landscape of immunotherapy.
BACKGROUND
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.


METHODS
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.


CONCLUSIONS
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.
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 ; mcriscitiello@cvm.tamu.edu.
Michael F
MF
Criscitiello
D000818:Animals; D015195:Drug Design; D006801:Humans; D007167:Immunotherapy; D009369:Neoplasms / Q000188:drug therapy; D011946:Receptors, Antigen / Q000276:immunology*; D012754:Sharks / Q000276:immunology*
D011946:Receptors, Antigen
T cell receptor; antibody; antigen receptor; immunology; shark