Antibodies: Timeline of key events

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Cesar Milstein and David Murray from Sera-Lab agree partner to commercially distribute cells for producing monoclonal antibodies to meet the worldwide requests flooding into Milstein's laboratory for access to such cells. 1977-02-01T00:00:00+0000Together with Australian immunologist, the Argentinian biochemist Cesar Milstein and Italian biochemist Giovanni Galfre develop monoclonal antibodies against rat histocompatibility antigens. This research demonstrates the practical applications of monoclonal antibodies for the first time, opening the way to their use for tissue typing for organ transplants. he work is published as A. F. Williams, G. Galfre, C. Milstein, 'Analysis of Cell Surfaces by Xenogeneic Myeloma-Hybrid Antibodies Differentiation Antigens of Rat Lymphocytes', Cell 12 (Nov 1977), 663-73. This paper would go on to cited in more than 1,490 publications by 1993. 1977-04-01T00:00:00+0000Hilary Koprowski, Polish born virologist and Carlo Croce, Italian born geneticist, both based at the Wistar Institute, file for the first US patent for monoclonal antibodies. The antibodies are made against viral antigens using cells supplied from Milstein's laboratory in September 1976. 1977-06-01T00:00:00+0000Argentinian biochemist Cesar Milstein, Italian biochemist Giovanni Galfre, and Australian scientist Alan Williams publish technique for the development of monoclonal antibodies against unknown rat cell surface antigens, predicting it will be possible to make monoclonals against any sort of cell surface molecule. The publication marks the beginning of the major use of monoclonals for understanding cellular function and disease. The article is published as A.F. Williams, G. Galfre and C. Milstein, 'Analysis of cell surfaces by xenogeneic myeloma-hybrid antibodies: Differentiation antigens of rat lymphocytes', Cell, 12/3 (1 Nov 1977), 663-73.1977-11-01T00:00:00+0000Ivor Royston, British-American onclologist together with American scientist Howard Birndorf set up Hybritech in San Diego. Hybritech is the first American company established to commercialise monoclonal antibodies for medical diagnostics and therapeutics. 1978-01-01T00:00:00+0000Argentinian biochemist Cesar Milstein and British immunologist Andrew McMichael produce the first monoclonal antibodies that target human T-cells. This lays the foundation for new understandings of the immune responses and disease. While initially rejected for publication, this work is published in A.J. McMichael, J.R. Pitch, J.W. Fabre, David Y. Mason, G. Galfre, 'A human thymocyte antigen defined by a hybrid myeloma monoclonal antibody', European Journal of Immunology, 9/3 (March 1979), 205-210. 1978-01-01T00:00:00+0000Cesar Milstein and Alan Williams generate a monoclonal antibody that targets blood group A cells. 1978-01-01T00:00:00+0000Sera-Lab, a British company specialising in antiserum, issues its first catalogue advertising monoclonal antibody cells from Milstein's laboratory. It represents the first commercialisation of monoclonal antibodies. 1978-02-01T00:00:00+0000Hilary Koprowski, Polish-born virologist and director of the Wistar Institute, together with American entrepreneur Michael Wall establish Centocor with Dutch-born biochemist Hubert Schoemaker and American scientist Ted Allen. Located in Philadelphia, Centocor is the second American company established to commercialise monoclonal antibodies for medical diagnostics and therapeutics.1979-05-01T00:00:00+0000Hilary Koprowski, Polish-born virologist, and colleagues granted US patent for monoclonal antibodies against tumour antigens (US Patent 4,172,124). The patent helps in the building of Centocor, the second American biotechnology set up to commercialise monoclonal antibodies. It also causes a major political controversy in Britain as the patent makes broad claims, essentially patenting the technique first developed by Cesar Milstein and George Kohler in 1975.1979-10-01T00:00:00+0000The British scientist, David Secher, based at the Laboratory of Molecular Biology in Cambridge, together with Derek Burke, a British scientist at Warwick University, create the first monoclonal antibody suitable for purifying interferon. This lays the foundation for the use of monoclonal antibodies as tools for the purification of human therapeutic proteins and other natural compounds.1980-01-01T00:00:00+0000Milstein suggests at a Wellcome Foundation lecture that by using genetic engineering scientists might be able to design tailor-made monoclonal antibodies that mimic antibodies made by the human body. This would free them up from a dependence on rodents for producing monoclonal antibodies. He publishes the idea in C. Milstein, 'Monoclonal antibodies from hybrid myelomas: Wellcome Foundation Lecture 1980', Proceedings Royal Society of London, 211 (1981), 393-412.1980-01-01T00:00:00+0000Referred to as Campath-1 (CAMbridge Pathology) family of antibodies, these are the first set of monoclonal antibodies against human lymphocytes derived from a rat. 1980-01-01T00:00:00+0000Spinks Report on Biotechnology points finger at Cesar Milstein and his colleagues for not attempting to patent the technique for producing monoclonal antibodies.1980-07-03T00:00:00+0000Tests begin with 17-1A, also known as edrecolomab, a monoclonal antibody developed at the Wistar Institute. 1980-12-01T00:00:00+0000Philip Karr, a patient with lymphoma, is treated by Ron Levy at Stanford University with a customised monoclonal antibody. It marks the first time a monoclonal antibody successfully treats cancer in a patient.1981-01-01T00:00:00+0000Held in Paris, the international workshop on human differentiation helped formulate a system for classifying monoclonals and bring out standardisation. Importantly it established a system based on identifying monoclonals found clustered around specific antigens. This laid the foundation for the CD nomeclature which has become a univeral tool for scientists to share and exchange knowledge about immune responses and disease. 1982-01-01T00:00:00+0000Encouraged by Cesar Milstein, collaborative research undertaken by Steven Sacks, Edwin Lennox and Douglas Voak produces monoclonal antibodies suitable for patenting and commercialisation for routine blood typing. 1982-01-01T00:00:00+0000JP Allison, BW McIntyre, D Bloch, 'Tumor-specific antigen of murine T-lymphoma defined with monoclonal antibody', Journal Immunology, 129 (1982), 2293.1982-11-01T00:00:00+0000Argentinian scientists Cesar Milstein and Claudio Cuello demonstrate the feasibility of creating bispecific monoclonal antibodies for use in immunohistochemistry, but application for patent, filed in 1983, is abandoned as result of prior patent promoting theory of such a technique. 1983-01-01T00:00:00+0000
Date Event People Places Sciences
Feb 1977Partnership begun for first commercial distribution of cells for producing monoclonal antibodiesMilstein, Murray Monoclonal antibodies
1977Monoclonals produced against histocompatibility antigensMilstein, Galfre, HowardLaboratory of Molecular Biology, Brabraham InstituteMonoclonal antibodies
Jun 1977First US patent application filed for monoclonal antibodiesCroce, Koprowski, MilsteinWistar InstituteMonoclonal antibodies
1977Monoclonal antibodies made to unknown cell surface antigensMilstein, Galfre, WilliamsLaboratory of Molecular Biology, Sir William Dunn School of PathologyMonoclonal antibodies
1978Hybritech foundedRoyston, Birndoff, GreeneSan DiegoMonoclonal antibodies
1978First monoclonal antibodies generated to human T-cellsMilstein, McMichaelLaboratory of Molecular Biology, Oxford UniversityMonoclonal antibodies
1978First monoclonal antibody generated for blood typingMilsteinLaboratory of Molecular Biology, Oxford UniversityMonoclonal antibodies
Feb 1978First commercialisation of monoclonal antibodies as laboratory reagentsMilstein, MurrayLaboratory of Molecular Biology, Sera-LabMonoclonal antibodies
May 1979Centocor foundedKoprowski, Schoemaker, WallWistar InstituteMonoclonal antibodies
Oct 1979First US patent for monoclonal antibodies grantedKoprowski, MilsteinWistar InstituteMonoclonal antibodies
Jan 1980First monoclonal antibody created to purify a human therapeutic protein.Burke, Milstein, SecherLaboratory of Molecular Biology, Warwick UniversityMonoclonal antibodies
1980Cesar Milstein proposed the use of recombinant DNA to improve monoclonal antibodiesMilsteinLaboratory of Molecular BiologyMonoclonal antibodies, Recombinant DNA
1980First monoclonal antibodies developed against T-cells which can also activate human complement.Waldmann, Cobbold, Hale, Metcalfe. Watt, TrangCambridge UniversityMonoclonal antibodies, Campath
1980British government commissioned report publically criticises non-patenting of technique for producing monoclonal antibodiesMilstein Monoclonal antibodies
Dec 1980Clinical tials begin with a monoclonal antibody for the treatment of gastrointestinal cancerKoprowskiWistar InstituteMonoclonal antibodies
1981First patient successfully treated with anti-idiotype monoclonal antibodyLevyStanford University Medical SchoolCancer immunotherapy, Monoclonal antibodies
1982First international workshop on human differentiation antigens establishes international code for classifying and coding monoclonal antibodiesBoumsell, BernardSaint-Louis HospitalMonoclonal antibodies
1982Monoclonal antibodies generated for routine use in ABO blood typingLennox, Milstein, Sacks, VoakLaboratory of Molecular Biology, Addenbrookes HospitalMonoclonal antibodies
Nov 1982James Allison and collegues use monoclonal antibody to provide first biochemical description of tumour specific antigen of murine T-lymphomaAllison, McIntyre, BlochUniversity of Texas System Cancer CenterImmunology, Cancer immunotherapy, Monoclonal antibodies, Oncology
1983First bispecific monoclonal antibody producedCuello, MilsteinLaboratory of Molecular Biology, Oxford UniversityMonoclonal antibodies

Feb 1977

Partnership begun for first commercial distribution of cells for producing monoclonal antibodies

1977

Monoclonals produced against histocompatibility antigens

Jun 1977

First US patent application filed for monoclonal antibodies

1977

Monoclonal antibodies made to unknown cell surface antigens

1978

Hybritech founded

1978

First monoclonal antibodies generated to human T-cells

1978

First monoclonal antibody generated for blood typing

Feb 1978

First commercialisation of monoclonal antibodies as laboratory reagents

May 1979

Centocor founded

Oct 1979

First US patent for monoclonal antibodies granted

Jan 1980

First monoclonal antibody created to purify a human therapeutic protein.

1980

Cesar Milstein proposed the use of recombinant DNA to improve monoclonal antibodies

1980

First monoclonal antibodies developed against T-cells which can also activate human complement.

1980

British government commissioned report publically criticises non-patenting of technique for producing monoclonal antibodies

Dec 1980

Clinical tials begin with a monoclonal antibody for the treatment of gastrointestinal cancer

1981

First patient successfully treated with anti-idiotype monoclonal antibody

1982

First international workshop on human differentiation antigens establishes international code for classifying and coding monoclonal antibodies

1982

Monoclonal antibodies generated for routine use in ABO blood typing

Nov 1982

James Allison and collegues use monoclonal antibody to provide first biochemical description of tumour specific antigen of murine T-lymphoma

1983

First bispecific monoclonal antibody produced