Cambridge University: Timeline of key events

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Work begins on the development of an anti-T-cell monoclonal antibody that can fix human complement to be used as a tool to prevent graft-versus-host disease in patients receiving bone marrow transplants. 1979-01-01T00:00:00+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+0000Waldmann is granted a programme grant to investigate the immunobiology of bone marrow transplantation.1980-01-01T00:00:00+0000The technique was developed by Martin Evans and Matt Kaufman. They showed that by delaying implantation it was possible to obtain slightly enlarged mouse blastocysts and that cells taken from these blastocysts could be used to establish mouse embryo stem cell cultures. The work was published in MJ Evans, MH Kaufman, 'Establishment in culture of pluripotential cells from mouse embryos', Nature, 292/154 (1981), 154-56.1981-07-09T00:00:00+0000Krebs was a biochemist who in 1933 was forced to leave Nazi Germany because his father was Jewish. He is best known for having discovered two important chemical reactions in the body - the urea cycle and the citric acid cycle. These chemical reactions help break down food molecules into carbon dioxide, water and energy. He made the breakthrough in the 1930s. The process is known as the Krebs cycle. Krebs was awarded the Nobel Prize in 1954.1981-11-22T00:00:00+0000The man treated is suffering from non-Hodgkin's lymphoma. While unable to prevent the death of the patient, the trial shows Campath-1M to be effective at depleting T-cells and well-tolerated.1982-01-01T00:00:00+0000The aim is to generate Campath monoclonal antibodies that can be infused directly into patients. 1983-01-01T00:00:00+0000G. Hale et al, 'Removal of T cells from bone marrow for transplantation: a monoclonal antilymphocyte antibody that fixes human complement', Blood, 62, (1983), 873-82.1983-10-25T00:00:00+0000The patient is being cared for by Martin Dyer and Frank Hayhoe. He is suffering from chronic lymphocytic leukaemia (CLL). Although the patient died shortly after treatment from his underlying disease, the result from the testing is promising. 1985-01-01T00:00:00+0000Campath-1G is seen as a possible means to reduce immunosuppressive drugs. Fears about the toxicity of the drug prevent work going any further. 1985-01-01T00:00:00+0000Lehmann was a biochemist renowned for his studies on the distribution of abnormal haemoglobins in many different human populations. This grew out of his interest in anaemia, begun when he served as assistant director of pathology to the North East India Command between 1942 and 1947. He helped to discover a high incidence in the sickle-cell trait in several aboriginal southern Indian populations. Based on his work he hypothesised that the gene for the trait could have been brought to Africa from India during prehistoric migrations.1985-07-13T00:00:00+0000Campath-1G is humanised, resulting in Campath-1H. It is accomplished with technology developed by Greg Winter.1988-01-01T00:00:00+0000This patent is filed on the basis of work reported in M Brüggeman, HM Caskey, C Teale, H Waldmann, Williams, Surani, and MS Neuberger, A repertoire of monoclonal antibodies with human heavy chains from transgenic mice, Proc Natl Acad Sci USA, 86 (Sept 1989), 6709-13. 1988-01-01T00:00:00+0000The patient is a 69 year old woman suffering from non-Hodgkin's lymphoma. The drug dramatically improves her health. 1988-01-01T00:00:00+0000Patients show marked improvements with the drug.1988-11-01T00:00:00+0000The aim of the centre is to facilitate the production of Campath and other monoclonal antibodies for clinical testing.1990-09-01T00:00:00+0000The research is undertaken by John Isaacs in collaboration with Brian Hazelman at Addenbrooke's Hospital.1991-01-01T00:00:00+0000Herman Waldmann and Alastair Compston begin a collaboration to test Campath-1H for treating multiple sclerosis (MS).1991-01-01T00:00:00+0000The drug dramatically improves the patient's condition.1991-01-01T00:00:00+0000Gwei-djen was a Chinese biochemist who undertook pioneering work on metabolic pathways. In 1933, Gwei-djen took the bold decision to leave China, then isolated from the West, to study for a doctorate at Cambridge University where she remained for the rest of her career. By 1939 she had developed the first sensitive assay for detecting low levels of pyruvic acid, an intermediate involved in the breakdown of carbohydrates. Her work demonstrated that the levels of pyruvic acid could be raised by vitamin B1 deficiency and exercise. Gwei-djen worked closely with both Dorothy and Joseph Needham. Together with Joseph she compiled a series of books detailing Chinese achievements in science and technology. 1991-11-28T00:00:00+0000
Date Event People Places Sciences
1979Waldmann is joined in his work by Stephen Cobbold, Geoff Hale, Alan Munro, Don Metcalfe, Suzanne Watt and Hoang Trang.Waldmann, Cobbold, Hale, Metcalfe. Watt, TrangCambridge UniversityCampath
1980First monoclonal antibodies developed against T-cells which can also activate human complement.Waldmann, Cobbold, Hale, Metcalfe. Watt, TrangCambridge UniversityMonoclonal antibodies, Campath
1980Waldmann gains MRC funding.WaldmannCambridge UniversityCampath
9 Jul 1981Mouse embryonic stem cells first isolated and cultured in the laboratoryEvans, Kaufman, MartinCambridge UniversityStem cells, Reproduction
22 Nov 1981Hans Adolf Krebs diedKrebsUniversity of Freiburg, Cambridge University, Sheffield University, Oxford UniversityCell, Biochemistry
1982The first patient is treated with Campath-1M.Waldmann, Swirsky, HayhoeCambridge UniversityCampath
1983 - 1985Efforts turn to generating IG Campath monoclonal antibodies.Waldmann, Hale, CobboldCambridge UniversityCampath
Oct 1983Publication of experiments indicating Campath-1 (alemtuzumab) monoclonal antibody activates complement and eliminate T-cellsWaldmann, Cobbold, Hale, Metcalfe. Watt, TrangCambridge UniversityCampath
1985Campath-1G is tested in the first patient.Waldmann, Hayhoe, DyerCambridge UniversityCampath
1985Campath-1G is explored on a small scale for the management of organ transplants by Roy Calne, a British transplant surgeon based at Addenbrooke's hospitalWaldmann, CalneCambridge UniversityCampath
13 Jul 1985Hermann Lehmann diedLehmannSt Bartholomew's Hospital, Cambridge UniversityBiochemistry, Haematology
1988Campath-1H is created - the first clinically useful humanised monoclonal antibody.Winter, Waldmann, Reichmann, ClarkCambridge University, Laboratory of Molecular BiologyMonoclonal antibodies, Recombinant DNA, Campath
1988Patent application filed for a method to create transgenic mice for the production of human antibodiesBruggeman, Caskey, Neuberger, Surani, Teale, Waldmann, WilliamsLaboratory of Molecular Biology, Babraham Institute, Cambridge UniversityMonoclonal antibodies, Cloning, Transgenic animals
1988Campath-1H is tested in the first humanWaldmann, Hale, Dyer, HayhoeCambridge UniversityCampath
Nov 1988Martin Lockwood, a clinician at Addenbrooke's Hospital, begins testing Campath-1H in patients with vasculitis.Lockwood, Hale, WaldmannCambridge UniversityCampath
Sep 1990The Therapeutic Antibody Centre (TAC) opens in the Regional Transfusion Centre at Addenbrooke's Hospital.Waldmann, HaleCambridge UniversityCampath
1991Campath-1H begins to be tested in patients with rheumatoid arthritis (RA)Isaacs, Hazleman, Hale, WaldmannCambridge UniversityCampath
1991Herman Waldmann and Alastair Compston begin a collaboration to test Campath-1H for treating multiple sclerosis (MS).Waldmann, Hale, CompstonCambridge UniversityCampath
1991The first MS patient is given Campath-1HWaldmann, hale, CompstonCambridge UniversityCampath
28 Nov 1991Lu Gwei-djen diedGwei-djenUniversity of CambridgeBiochemistry, Metabolism

1979

Waldmann is joined in his work by Stephen Cobbold, Geoff Hale, Alan Munro, Don Metcalfe, Suzanne Watt and Hoang Trang.

1980

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

1980

Waldmann gains MRC funding.

9 Jul 1981

Mouse embryonic stem cells first isolated and cultured in the laboratory

22 Nov 1981

Hans Adolf Krebs died

1982

The first patient is treated with Campath-1M.

1983 - 1985

Efforts turn to generating IG Campath monoclonal antibodies.

Oct 1983

Publication of experiments indicating Campath-1 (alemtuzumab) monoclonal antibody activates complement and eliminate T-cells

1985

Campath-1G is tested in the first patient.

1985

Campath-1G is explored on a small scale for the management of organ transplants by Roy Calne, a British transplant surgeon based at Addenbrooke's hospital

13 Jul 1985

Hermann Lehmann died

1988

Campath-1H is created - the first clinically useful humanised monoclonal antibody.

1988

Patent application filed for a method to create transgenic mice for the production of human antibodies

1988

Campath-1H is tested in the first human

Nov 1988

Martin Lockwood, a clinician at Addenbrooke's Hospital, begins testing Campath-1H in patients with vasculitis.

Nov 1988

The Therapeutic Antibody Centre (TAC) opens in the Regional Transfusion Centre at Addenbrooke's Hospital.

1991

Campath-1H begins to be tested in patients with rheumatoid arthritis (RA)

1991

Herman Waldmann and Alastair Compston begin a collaboration to test Campath-1H for treating multiple sclerosis (MS).

1991

The first MS patient is given Campath-1H

28 Nov 1991

Lu Gwei-djen died

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