期刊论文详细信息
Infectious Diseases of Poverty
Leishmania tarentolae: an alternative approach to the production of monoclonal antibodies to treat emerging viral infections
Joshua D Jones1 
[1]Division of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK
关键词: Therapy;    Monoclonal;    Leishmania;    Infection;    Expression;    Emerging;    Ebola;    Antibody;   
Others  :  1216860
DOI  :  10.1186/2049-9957-4-8
 received in 2014-11-26, accepted in 2015-01-13,  发布年份 2015
PDF
【 摘 要 】

Background

Monoclonal antibody therapy has an important role to play as a post-exposure prophylactic and therapeutic for the treatment of viral infections, including emerging infections. For example, several patients of the present Ebola virus outbreak in West Africa were treated with ZMapp, a cocktail of three monoclonal antibodies which are expressed in Nicotiana benthamiana.

Discussion

The majority of monoclonal antibodies in clinical use are expressed in mammalian cell lines which offer native folding and glycosylation of the expressed antibody. Monoclonal antibody expression in vegetal systems offers advantages over expression in mammalian cell lines, including improved potential for scale up and reduced costs. In this paper, I highlight the advantages of an upcoming protozoal system for the expression of recombinant antibody formats. Leishmania tarentolae offers a robust, economical expression of proteins with mammalian glycosylation patterns expressed in stable cell lines and grown in suspension culture. Several advantages of this system make it particularly suited for use in developing contexts.

Summary

Given the potential importance of monoclonal antibody therapy in the containment of emerging viral infections, novel and alternative strategies to improve production must be explored.

【 授权许可】

   
2015 Jones; licensee BioMed Central.

【 预 览 】
附件列表
Files Size Format View
20150703093039934.pdf 345KB PDF download
Figure 1. 65KB Image download
【 图 表 】

Figure 1.

【 参考文献 】
  • [1]Scott AM, Wolchok JD, Old LJ: Antibody therapy of cancer. Nat Rev Cancer 2012, 12(4):278-87.
  • [2]Chan AC, Carter PJ: Therapeutic antibodies for autoimmunity and inflammation. Nat Rev Immunol 2010, 10(5):301-16.
  • [3]Casadevall A, Dadachova E, Pirofski LA: Passive antibody therapy for infectious diseases. Nat Rev Microbiol 2004, 2(9):695-703.
  • [4]Reichert JM: Metrics for antibody therapeutics development. In MAbs. Volume 2. United States: Landes Biosciences; 2010::695-700.
  • [5]Imai K, Takaoka A: Comparing antibody and small-molecule therapies for cancer. Nat Rev Cancer 2006, 6(9):714-27.
  • [6]Murphy K, Travers P, Walport M: Janeway’s immunobiology. 7th edition. New York: Garland Science; 2008.
  • [7]Holliger P, Hudson PJ: Engineered antibody fragments and the rise of single domains. Nat Biotechnol 2005, 23(9):1126-36.
  • [8]Bird RE, Hardman KD, Jacobson JW, Johnson S, Kaufman BM, Lee SM, Lee T, Pope SH, Riordan GS, Whitlow M: Single-chain antigen-binding proteins. Science 1988, 242(4877):423-6.
  • [9]Ahmad ZA, Yeap SK, Ali AM, Ho WY, Alitheen NB, Hamid M: scFv antibody: principles and clinical application. Clin Dev Immunol 2012, 2012:980250.
  • [10]Li B, Ye J, Lin Y, Wang M, Zhu J: Preparation and identification of a single-chain variable fragment antibody against Newcastle diseases virus F48E9. Vet Immunol Immunopathol 2014, 161(3–4):258-64.
  • [11]Frenzel A, Hust M, Schirrmann T: Expression of recombinant antibodies. Front Immunol 2013, 4:217.
  • [12]Powers DB, Amersdorfer P, Poul M, Nielsen UB, Shalaby MR, Adams GP, Weiner LM, Marks JD: Expression of single-chain Fv-Fc fusions in Pichia pastoris. J Immunol Methods 2001, 251(1–2):123-35.
  • [13]Rulker T, Voss L, Thullier P, LM OB, Pelat T, Perkins SD, Langermann C, Schirrmann T, Dubel S, Marschall HJ, et al.: Isolation and characterisation of a human-like antibody fragment (scFv) that inactivates VEEV in vitro and in vivo. PLoS One 2012, 7(5):e37242.
  • [14]Sawyer LA: Antibodies for the prevention and treatment of viral diseases. Antiviral Res 2000, 47(2):57-77.
  • [15]Bossart KN, Geisbert TW, Feldmann H, Zhu Z, Feldmann F, Geisbert JB, Yan L, Feng YR, Brining D, Scott D, et al.: A neutralizing human monoclonal antibody protects african green monkeys from hendra virus challenge. Sci Transl Med 2011, 3(105):105ra103.
  • [16]Hendra virus, equine - Australia (05): (Queensland), human exposure. (International Society for Infectious Diseases, archive no. 20100527.1761. 2010. http://www.promedmail.org webcite
  • [17]Qiu X, Wong G, Audet J, Bello A, Fernando L, Alimonti JB, Fausther-Bovendo H, Wei H, Aviles J, Hiatt E, et al.: Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp. Nature 2014, 514(7520):47-53.
  • [18]Ebola virus disease - ex Africa (40): USA ZMapp, cost, UK, India prevention. (International Society for Infectious Diseases, archive no. 20141119.2972218). 2014. http://www.promedmail.org webcite
  • [19]Sodoyer R: Expression systems for the production of recombinant pharmaceuticals. BioDrugs 2004, 18(1):51-62.
  • [20]Gomord V, Chamberlain P, Jefferis R, Faye L: Biopharmaceutical production in plants: problems, solutions and opportunities. Trends Biotechnol 2005, 23(11):559-65.
  • [21]Jin C, Altmann F, Strasser R, Mach L, Schahs M, Kunert R, Rademacher T, Glossl J, Steinkellner H: A plant-derived human monoclonal antibody induces an anti-carbohydrate immune response in rabbits. Glycobiology 2008, 18(3):235-41.
  • [22]Zeitlin L, Pettitt J, Scully C, Bohorova N, Kim D, Pauly M, Hiatt A, Ngo L, Steinkellner H, Whaley KJ, et al.: Enhanced potency of a fucose-free monoclonal antibody being developed as an Ebola virus immunoprotectant. Proc Natl Acad Sci U S A 2011, 108(51):20690-4.
  • [23]Strasser R, Stadlmann J, Schahs M, Stiegler G, Quendler H, Mach L, Glossl J, Weterings K, Pabst M, Steinkellner H: Generation of glyco-engineered Nicotiana benthamiana for the production of monoclonal antibodies with a homogeneous human-like N-glycan structure. Plant Biotechnol J 2008, 6(4):392-402.
  • [24]Wacker M, Linton D, Hitchen PG, Nita-Lazar M, Haslam SM, North SJ, Panico M, Morris HR, Dell A, Wren BW, et al.: N-linked glycosylation in Campylobacter jejuni and its functional transfer into E. coli. Science 2002, 298(5599):1790-3.
  • [25]Raymond F, Boisvert S, Roy G, Ritt JF, Legare D, Isnard A, Stanke M, Olivier M, Tremblay MJ, Papadopoulou B, et al.: Genome sequencing of the lizard parasite Leishmania tarentolae reveals loss of genes associated to the intracellular stage of human pathogenic species. Nucleic Acids Res 2012, 40(3):1131-47.
  • [26]Simpson L, Aphasizhev R, Gao G, Kang X: Mitochondrial proteins and complexes in Leishmania and Trypanosoma involved in U-insertion/deletion RNA editing. RNA 2004, 10(2):159-70.
  • [27]White TC, Fase-Fowler F, van Luenen H, Calafat J, Borst P: The H circles of Leishmania tarentolae are a unique amplifiable system of oligomeric DNAs associated with drug resistance. J Biol Chem 1988, 263(32):16977-83.
  • [28]Breton M, Zhao C, Ouellette M, Tremblay MJ, Papadopoulou B: A recombinant non-pathogenic Leishmania vaccine expressing human immunodeficiency virus 1 (HIV-1) Gag elicits cell-mediated immunity in mice and decreases HIV-1 replication in human tonsillar tissue following exposure to HIV-1 infection. J Gen Virol 2007, 88(Pt 1):217-25.
  • [29]Breitling R, Klingner S, Callewaert N, Pietrucha R, Geyer A, Ehrlich G, Hartung R, Muller A, Contreras R, Beverley SM, et al.: Non-pathogenic trypanosomatid protozoa as a platform for protein research and production. Protein Expr Purif 2002, 25(2):209-18.
  • [30]Klatt S, Rohe M, Alagesan K, Kolarich D, Konthur Z, Hartl D: Production of glycosylated soluble amyloid precursor protein alpha (sAPPalpha) in Leishmania tarentolae. J Proteome Res 2013, 12(1):396-403.
  • [31]Fritsche C, Sitz M, Weiland N, Breitling R, Pohl HD: Characterization of the growth behavior of Leishmania tarentolae: a new expression system for recombinant proteins. J Basic Microbiol 2007, 47(5):384-93.
  • [32]Kushnir S, Gase K, Breitling R, Alexandrov K: Development of an inducible protein expression system based on the protozoan host Leishmania tarentolae. Protein Expr Purif 2005, 42(1):37-46.
  • [33]Bolhassani A, Taheri T, Taslimi Y, Zamanilui S, Zahedifard F, Seyed N, Torkashvand F, Vaziri B, Rafati S: Fluorescent Leishmania species: development of stable GFP expression and its application for in vitro and in vivo studies. Exp Parasitol 2011, 127(3):637-45.
  • [34]Jorgensen ML, Friis NA, Just J, Madsen P, Petersen SV, Kristensen P: Expression of single-chain variable fragments fused with the Fc-region of rabbit IgG in Leishmania tarentolae. Microb Cell Fact 2014, 13:9. BioMed Central Full Text
  • [35]Lai T, Yang Y, Ng SK: Advances in Mammalian cell line development technologies for recombinant protein production. Pharmaceuticals (Basel) 2013, 6(5):579-603.
  文献评价指标  
  下载次数:6次 浏览次数:7次