The development of hybridoma technology in 1975 by the two scientists, Kohler and Milstein, has opened a new era for production of specific antibodies in diagnosis, treatment and prevention of diseases both in animals and humans. Since then, many scientists have worked much in the field of antibody cloning and fragmentation technique to produce a very specific antibody called monoclonal antidody which is very usefull in the disease combating activity. An antibody is a large Y-shaped glycoprotein produced by B-cells. Therapeutic antibodies represent one of the fastest growing areas of the pharmaceutical industry. Antibodies have been engineered by a variety of methods to suit a particular therapeutic use. Hybridomas are cells that have been engineered to produce a desired antibody in large amounts, to produce monoclonal antibodies. Mouse antibodies have been reengineered in vitro to replace framework amino acid residues with corresponding human sequences through antibody fragment engineering. For use of antibodies as therapeutics, a diversity of engineered antibody forms have been created to improve their efficacy, including enhancing effector functions of full-length antibodies, delivering toxins to kill cells or cytokines in order to stimulate immune system, bispecific antibodies to target multiple receptors, and intrabodies to interfere and inhibit cellular processes inside cells in a number of ways. One technology that has been explored to generate low immunogenicity of monoclonal antibodies (mAbs) for in vitro therapy involves the use of transgenic animals and plants expressing repertories of the target antibody gene sequences. This technology has now been exploited by over a dozen different pharmaceutical and biotechnology companies toward developing new therapy mAbs. Now a days, scientists are using transgenic animals and plants to produce specific antibodies (monoclonal antibodies) and are showing an innovative promise in future to solve many disease cost problems both in animal and human. However, the use and industrial production of monoclonal antibodies through the application of antibody engineering is still less than the expected value, mostly in developing country’s including Ethiopia.
A Review on: Antibody Engineering for Development of Therapeutic Antibodies, International Journal of Immunology.
Vol. 3, No. 3,
2015, pp. 27-36.
Adams, G. P., Schier, R., Marshall, K., Wolf, E. J., McCall, A. M., Crawford, E.J., Weiner, L.M. (1998): Increased affinity leads to improved selective tumor delivery of single-chain Fv antibodies. Cancer Res., 58: 485–490.
Barclay A. (2003): "Membrane proteins with immunoglobulin-like domains - a master superfamily of interaction molecules". Semin Immunol, 15 (4): 215–223.
Better, M., Chang, C.P., Robinson, R.R., Horwitz, A.H. (1988): Escherichia coli secretion of an active chimeric antibody fragment. Science, 240: 1041-1043.
Borghesi L and Milcarek C. (2006): "From B cell to plasma cell: regulation of V(D)J recombination and antibody secretion". Immunol. Res. 36 (1–3): 27–32.
Bretton, PR, Melamed, MR, Fair, WR, Cote, RJ (1994): Detection of occult micrometastases in the bone marrow of patients with prostate carcinoma. Prostate, 25(2): 108-114.
Cabanes-Macheteau, M., Fitchette-Laine, A.C., Loutelier-Bourhis, C., Lange, C., Vine, N., Ma, J. (1999): N-Glycosylation of a mouse IgG expressed in transgenic tobacco plants. Glycobiology, 9:365–372.
Cao, Y. and Suresh, M.R.(1998): Bispecific antibodies as novel bioconjugates. Bioconjug. Chem.,9: 635-644.
Cardoso,D.F., Nato, F., England, P., Ferreira, M.L., Vaughan, T.J., Mota, I., Mazie, J.C., Choumet,V., Lafaye, P. (2000): Scand. J. Immunol, 51: 337–344.
Chang, C. H., Sharkey, R. M., Rossi, E. A., Karacay, H., and McBride.(2002): Molecular advances in pretargeting radioimunotherapy with bispecific antibodies. Mol. Cancer Ther, 1: 553–563.
Charles Janeway (2001). Immunobiology. (5th ed.). Garland Publishing. ISBN 0-8153-3642-X.
Chapman A. P. (2002): PEGylated antibodies and antibody fragments for improved therapy: a review. Adv. Drug Deliv. Rev, 54: 531–545.
Craig, P. S., Hocking, R. E., Mitchell, G. F. and Rechard, M. D. (1981), Murine hybridoma-derived antibodies in the processing of antigens for the immune diagnosis of Echinococcus granulosus infection in sheep. Parasitology, 83(2): 303-17.
Dall’Acqua, W. F., Woods, R. M., Ward, E. S., Palaszynski, S. R., Patel, and N. K. (2002): Increasing the affinity of a human IgG1 for the neonatal Fc receptor: Biological consequences. J. Immunol, 169: 5171–5180.
Danforth, H. D. (1986), Use of hybridoma antibodies combined with genetic engineering in the study of protozoan parasites: A review. In: L.P.Joiner, P.L. Long and L. R. McDongald (Ed.) proc. Georgia coccidiosis conf., P574.
Diaz M and Casali P. (2002): "Somatic immunoglobulin hypermutation". Curr Opin Immunol, 14 (2): 235–240.
Duenas, M. and Borrebaeck C. A. (1994): Clonal selection and amplification of phage displayed antibodies by linking antigen recognition and phage replication. Bio-Technology, 12: 999–1002.
Dunham, I., N. Shimizu, B.A. Roe, S. Chissoe.A.R. Hunt, J.E. Collins, R. Bruskiewich and D.M. Beare. (1999): The DNA sequence of human chromosome 22. Nature, 402:489-495.
Fischer N. and Leger O. (2007): Bispecific antibodies: molecules that enable novel therapeutic strategies. Pathobiology. ;74:3–14.
Fugmann SD, Lee AI, Shockett PE, Villey IJ, schatz DG. (2000): the RAG proteins and V(D)J recombination: complexes, ends, transposition.
Gamble, H.R., Anderson, W.R., Graham, C.E. and Murell, K.D. (1983), monoclonal antibody-purified antigen for the immune diagnosis of trichinosis. Am. J. Vet. Res., 45:67.
Gellert M. V(D)J recombination. (2002): RAG proteins, repair factores, and regulation.
Giritch A, Marillonnet S, Engler C, van Eldik G, Botterman J, Klimyuk V., Gleba, K., Makinen. (2006): Rapid high-yield expression of full-size IgG antibodies in plants coinfected with noncompeting viral vectors. Proc Natl Acad Sci USA. ;103:14701–14706.
Graumann K, Premstaller A. (2006): Manufacturing of recombinant therapeutic proteins in microbial systems. Biotechnol J. ;1:164–186.
Graus Porta D, Beerli RR and Hynes NE,( 1995): Intrabodies Valuable Tools for Target Validation. Mol Cell Biol, 15:182-191.
Harris and B. (1999): Exploiting antibody-based technologies to manage environmental pollution. Trend.s Biotechnol. 17: 290-296.
Ho, M., Kreitman, R. J., Onda, M., and Pastan, I. (2005): In vitro antibody evolution targeting germline hot spots to increase activity of an anti-CD22 immunotoxin. J. Biol. Chem, 280: 607–617.
Holliger PT, Prospero T and Winter G. (1993): Diabodies : small biavalent and bispecific antibody fragments proc. Nati Acad Sci USA, 90: 6444-6448.
Hoogenboom, H. R. and Winter G. (1992): Bypassing immunisation. Human antibodies from synthetic repertoires of germline VH gene segments rearranged in vitro. J. Mol. Biol, 227: 381–388.
King, D. J., Turner, A., Farnsworth, A. P., Adair, J. R and Owens, R. J. (1994): Improved tumor targeting with chemically cross-linked recombinant antibody fragments. Cancer Res, 54: 6176–6185.
Kohler G, Milstein C. (1975): Continuous cultures of fused cells secreting antibody of predefined specificity.Nature. ;256:495–97.
Kuby.J. (2007): Kuby Immunology, W.H.Freeman and Company, New York
Lazikani B, Lesk AM, Chothia C. (1997): "Standard conformations for the canonical structures of immunoglobulins". J Mol Biol, 273 (4): 927–948.
Larrick, J.W., L. Yu, J. Chen, S. Jaiswal and K. Wycoff. (1998): Production of antibodies in transgenic plants. Res. Immunol, 149: 603-608.
Le Gall, F., Kipriyanov, S.M., Moldenhauer, G. and Little M. (1999): Di-, tri- and tetrameric single chain Fv antibody fragments against human CD19: e¡ect of valency on cell binding. FEBS Lett, 453: 164-168.
Lo AS, Zhu Q, Marasco WA. (2008): Intracellular antibodies (intrabodies) and their therapeutic potential. In: Chernajovsky Y, Nissim A, editors. Therapeutic Antibodies. Handbook of Experimental Pharmacology, Volume 181. Berlin Heidelberg: Springer-Verlag;. pp. 343–373. Eds.
Lyer Y.S., Vasantha k., Manisha P., Jadhav S., Gupte S.C. and Mohanty D.( 2006): Production of murine monoclonal anti-B, Indian J Med Res, 123: 561- 564.
Market E and Papavasiliou F. (2003): "V (D) J recombination and the evolution of the adaptive immune system". PLoS Biol. 1 (1): E16.
Maynard, J. A., Maassen, C. B., Leppla, S. H., Brasky, K., Patterson and J. L. (2002): Protection against anthrax toxin by recombinant antibody fragments correlates with antigen affinity. Nat. Biotechnol, 20: 597–601.
Mian I, Bradwell A and Olson A. (1991): "Structure, function and properties of antibody binding sites Olson AJ.J Mol Biol.1991 Jan 5; 217 (1): 133–151.
Milstein. C. (1999): "The hybridoma revolution: an offshoot of basic research." Bioassays, 21 (11): 966–973.
Muller, B.H., Chevrier, D., Boulain, J.C. and Guesdon J.L. (1999): Recombinant single-chain Fv antibody fragment-alkaline phosphates conjugate for one-step immunodetection in molecular hybridization. J. Immunol. Methods, 227: 177-185.
Nelson, PN; Reynolds, GM; Waldron, EE; Ward, E; Giannopoulos, K; Murray and PG. (2000): "Demystified Monoclonal antibodies". Molecular pathology: MP, 53 (3): 111–117.
Nemazee D. (2006): "Receptor editing in lymphocyte development and central tolerance". Nat Rev Immunol, 6 (10): 728–740.
Neuberger, MS, Williams GT, Mitchell EB, Jouhal SS, Flanagan JG, Rabbitts TH. (2000); A hapten-specific chimaeric IgE antibody with human physiological effector function. Nature. 314:268–270.
North B, Lehmann A and Dunbrack RL. (2010): "A new clustering of antibody CDR loop conformations". J Mol Biol, 406 (2): 228–256.
Pasqualini, Renata and Arap Wadih. ( 2004): Hybridoma-free generation of monoclonal antibodies, PANS, 101: 257-259.
Pier GB, Lyczak JB and Wetzler LM. (2004): Immunology, Infection, and Immunity. ASM Press. ISBN 1-55581-246-5.
Ravetch J and Bolland S. (2001): "IgG Fc receptors". Annu Rev Immunol, 19 (1): 275–290.
Roux K. (1999): "Immunoglobulin structure and function as revealed by electron microscopy". Int Arch Allergy Immunol, 120 (2): 85–99.
Sang Jick Kim, Youngwoo Park, and Hyo Jeong Hong. (2005): Antibody Engineering for the Development of Therapeutic Antibodies. Mol. Cells Vol. 20, No. 1, pp. 17-29.
Sharmal, S.D., Araujo, F.G. and Remington, J.S. (1984), Toxoplasma antigen is isolated by affinity chromatography with monoclonal antibody protects mice against lethal infection with toxoplasma gondii.J.Immunol., 133:2818.
Spada, S., Krebber, C., and Pluckthun, A. (1997): Selectively infective phages (SIP) technology. Biol. Chem, 378: 445–456.
Steve Sensole. (2004): Transgenic technology for monoclonal antibody production. Novel technologies and therapeutic use, 2: 1-2.
Stavnezer J and Amemiya CT. (2004): "Evolution of isotype switching". Semin. Immunol, 16 (4): 257–275.
Tizard, Ian. R, 2004. Veterinary immunology an Introduction, Seventh edition.
Vaccaro DE, Markinac JE. (1995): Use of monoclonal antibodies with particles to separate cell subpopulations by positive selection. Methods Mol Biol. ;45:253–9.
Wabl, M., Cascalho, M., and Steinberg, C. (1999): Hypermutation in antibody affinity maturation. Curr. Opin. Immunol, 11: 186–189.
Ward, E. S., Gussow, D., Griffiths, A. D., Jones, P. T., and Winter G. (1989): Binding activities of a repertoire of single immunoglobulin variable domains secreted from Escherichia coli. Nature, 341: 544–546.
Waterhouse P., A. Griffiths, K. Johnson and G. Winter. (1993): Combinatorial infection and in vivo recombination: a strategy for making large phage antibody repertoires. Nucleic Acids Res, 21: 2265-2266.
Winter G and Milstein C. (1991): Man-made antibodies. Nature, 349: 293-299.
Williams, W.V., T. Kieber-Emmons, J. Von- Feldt, M.I. Greene and D.B. Weiner. (1991): Design of bioactive peptides based on antibody hypervariable region structures. J. Biol. Chem., 266: 5182-5190.
Zhang, M. Y., Shu, Y., Rudolph, D., Prabakaran, P., Labrijn, and A. F. (2004): Improved breadth and potency of an HIV-1- neutralizing human single-chain antibody by random mutagenesis and sequential antigen panning. J. Mol. Biol., 335: 209– 219.