Recombinant Antibodies and Their Potential Applications in Veterinary Medicine

INTRODUCTION

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The age of biotherapy in medicine is more than 30 years, but its introduction to veterinary medicine is relatively new. Many hormonal preparations are being extensively used in management of estrus and fertility in animal husbandry and veterinary sciences but the case is not similar with biotherapeutic antibodies. Production of biotherapeutic recombinant antibodies for different species suitable to be used clinically has been a limiting factor for many years, but discovery of hybridoma technology by Kohler and Milstein¹ heralded a new era for immunotherapy by facilitating production of various non-murine monoclonal antibodies². The production of such type of recombinant monoclonal antibodies has proven to be a tremendous leap in the field of biotherapy due to their potential use in diagnostics, prophylaxis and therapeutics. Orthoclone (Muromonab-CD3) is first monoclonal antibody to get FDA approval for human use in 1992 followed by 80 more monoclonal antibodies approved till today^2-4. Though the majority of monoclonal antibodies approved for biotherapy are devoted to humans, but advances in veterinary medicine are also exciting and inspiring. Especially, with the launch of first monoclonal antibody approved for veterinary use in the European Union States and United states for the treatment of Canine atopic dermatitis i.e., Cytopoint and lokivetmab, respectively. Cytopoint or lokivetmab neutralizes canine interleukin-31(IL-31) and treats the clinical signs of atopic dermatitis for a single injection angle injection. The IL-31 is the key protein for cell to cell communication and trigger’s pruritus, thus neutralizing IL-31only alleviates clinical signs of atopic dermatitis and don’t leads to any undue immune-suppression and immune-stimulation.

Success in the use of monoclonal antibody is aiding in the rapid understanding of their limitations and failures also, for example, even after three quarters of clinical trials on monoclonal antibody-drug conjugates on oncological malignancies, only minor success has been achieved in getting minor tissue penetration and target binding⁵. The reason being their cumbersome size and unfavorable chemical framework. To encounter such limitations and failures, various new recombinant antibody fragments (rAb) has been developed. These biotherapeutic recombinant antibodies include a single chain fragment variable (scFv), single-domain antibody or nanobodies, triabodies, tetrabodies and hybrid/chimeric recombinant antibodies. Of these types single chain fragment variable and nanobodies are two categories which has already been introduced and explored significantly in research in veterinary medicine⁶. Already there are some monoclonal antibody fragments approved in the United States like Certolizumab pegol (cimzia)-a anti-TNF alpha pegylated humanized Fab for Crohn disease, ranibizumab (lucentis)a anti-VEGF-humanized Fab for macular degeneration and abciximab (reopro) anti-GP IIb/IIIa chimeric Fab approved for clot prevention in angioplasty⁷. For animal diseases too, initial study has proven to be fruitful like two single chain fragment variables specific for 3ABC antigen has been reported to differentiate vaccinated and non-vaccinated FMD cattle successfully⁸. Similarly, a scFv-anticapsid protein showed better sensitivity in ELISA and western blot as compared to gold standard monoclonal antibodies⁹. Similarly nanobodies against Brucella mellitensis and bovine spongiform encephalopathy (BSE) successfully diagnosed Brucella and BSE^10,11. A nanobodies based detection of Taenia solium infection showed no cross reactivity with T. saginata, T. hydatigena, T. crassiceps and Trichenella spiralis¹².