Antibodies: Timeline of key events

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Ritxuan (rituiximab) is approved for the treatment of non-Hodgkin Lymphoma. The drug arose out of Ronald Levy's research for three decades to find a way of harnessing the power of the body's own immune system to fight cancer. 1997-01-01T00:00:00+0000Daclizumab was approved by the FDA for the preventition of acute rejection of kidney transplants. The monoclonal antibody was developed by Protein Design Labs using a humanising method devised by Cary Queen and marketed together with F. Hoffmann-La Roche. 1997-12-01T00:00:00+0000The drug is a monoclonal antibody that targets cancer cells that overproduce the HER2/neu oncoprotein1998-01-01T00:00:00+0000Remicade (infliximab) is approved for the treatment of Crohn's disease. Soon after Remicade wins approval for other autoimmune and inflammatory conditions including rheumatoid arthritis and ulcerative colitis. The drug, a monoclonal antibody against TNF alpha, a powerful promoter of inflammation, was developed in 1989 by Jan Vilcek and Jumning Le and developed in collaboration with Centocor, Marc Feldmann and Maini1998-08-01T00:00:00+0000Launched by the biotechnology company Medarex in collaboration with Jim Allison. 2000-01-01T00:00:00+0000Michael Smith shared the 1993 Nobel Prize for Chemistry for a technique that enables researchers to introduce specific mutations into genes and, thus, to the proteins that they encode. He developed the method, known as site-directed mutagenesis, in the 1970s, in collaboration with Fred Sanger and Clyde A Hutchinson III. The advantage of the technique was that it allowed comparisons to be made of different protein molecules and provide a means to deliberately alter a specific gene thereby making it possible to modify the characteristics of an organism. His work opened up a new chapter for studying and treating genetic diseases. Site-directed mutagenesis is a pivotal tool today in genetic and protein research and engineering and at the forefront of the development of monoclonal antibody drugs. 2000-10-04T00:00:00+0000Milstein was an Argentinian biochemist. Together with Georges Kohler, Milstein developed the first unlimited supply of long-lasting monoclonal antibodies. Their technique now underpins the development and application of many diagnostics and therapeutics. Kohler and Milstein devised the method as part of their search for a tool to investigate how the immune system can make so many different kinds antibodies, each able to bind to a highly specific receptor on foreign substances that invade the body. 2002-03-24T00:00:00+0000Adalimumab (Humira) approved by the FDA for the treatment of rheumatoid arthritis. The drug was developed and marketed by a collaboration between Cambridge Antibogy Technology, BASF Bioresearch Corporation and Abbott Laboratories.2002-12-31T00:00:00+0000Chase was an American immunologist who in the early 1940s discovered that white blood cells trigger the immune response in the body confronting a foreign invader. His finding laid to rest the belief that antibodies by themselves could protect the body from allergies and pathogens. Chase also uncovered the second arm of the immune system, known as cell-mediated immunity, paving the way to the discovery of lymphocyte cells and B and T cells.2004-01-05T00:00:00+0000The diagnostic, called NeutroSpectT, uses a monoclonal antibody, SSEA1, discovered at the Wistar Institute and developed by Palatin Technologies.2004-04-05T00:00:00+0000Murray was the founder of Sera-Lab, the first biotechnology company to commercialise monoclonal antibodies. His entrepreneurial efforts paved the way to the wide-scale adoption of monoclonal antibodies in research and their clinical application. 2004-10-11T00:00:00+0000The two companies agreed to share the costs and responsibilities of research and product development up to the completion of a Phase 2 clinical study in each party's territory.2005-05-01T00:00:00+0000Schoemaker was a Dutch biochemist who was co-founder and first Chief Executive Officer of Centocor, an American biotechnology company that pioneered the commercialisation of monoclonal antibody diagnostics and therapeutics. After Centocor was sold to Johnson & Johnson for $5.2 billion in 1999, Schoemaker founded Neuronyx to develop cellular therapies. One of the treatments pioneered by Neuronyx was the use of stem cells from bone marrow to help regenerate heart tissue damaged by heart attacks. 2006-01-01T00:00:00+0000Panitumumab (Vectibix) was approved by the FDA for the treatment of patients with EGFR-expressing metatastic colorectal cancer. The drug is a fully human monoclonal antibody created with transgenic mice. It was developed by Agensys with Amgen. 2006-09-27T00:00:00+0000Drug, MSX-1106, to be assessed for malignant melanoma, renal cell cancer, castrate-resistant prostate cancer and non-small cell lung carcinoma2008-11-24T00:00:00+0000Klinman was an American immunologist who developed the splenic focus assay, a tool that allowed analysis of antibody production derived from single clones of B cells. He used the tool to analyse immune tolerance and immune responses to influenza. In additon he invented the splenic fragment system, a technique that helped generate some of earliest monoclonal antibodies against viral antigens and cancer.2010-05-04T00:00:00+0000The drug was approved for the treatment of unresectable or metastatic melanoma. The drug uses a monoclonal that blocks CTLA-4 so as to activate an immune response against the cancer.2011-03-25T00:00:00+0000Alemtuzumab was originally developed by Herman Waldmann as a laboratory tool to investigate immune tolerance. It soon became the first humanised monoclonal antibody drug. Initially alemtuzumab proved effective for helping prevent graft-versus host disease in transplant patients. It subsequently went on to be approved as a treatment for leukaemia and then many years later it was shown to be effective against multiple sclerosis. 2013-09-17T00:00:00+0000A pioneer of antibody engineering, Neuberger developed some of the first techniques for the generation of chimeric and humanised antibodies. He also helped create the first transgenic mice for the production of human monoclonal antibodies. His work paved the way for the generation of safer and more effective monoclonal antibody drugs. 2013-10-26T00:00:00+0000Edelman was an American biologist renowned for his research on antibodies, the body's defense against harmful foreign substances like viruses and bacteria. His research helped determine the chemical structure of antibodies in the early 1960s. It showed that antibodies were made up of two light and heavy chains linked together by disulfide bonds. The breakthrough immediately galvanised feverish activity in all fields of immunological science, paving the way to the development of antibodies for both diagnostics and therapy. Edelman was awarded the Nobel Prize for Medicine in 1972 for his work. 2014-05-17T00:00:00+0000
Date Event People Places Sciences
1997FDA approved the first monoclonal antibody cancer drug for the American marketLevy, RastetterStanford University Medical School, Idec PharmaceuticalsCancer immunotherapy, Monoclonal antibodies
Dec 1997First humanised monoclonal antibody approved for marketQueenProtein Design Labs, RocheMonoclonal antibodies, Recombinant DNA
1998FDA approved Trastuzumab (Herceptin) for the treatment of metastatic breast cancer   Monoclonal antibodies, Oncology
Aug 1998FDA and European regulatory authorities approved the first monoclonal antibody drug for an autoimmune diseaseVilcek, Le, Feldmann, Maini, SchoemakerNew York University, Centocor, Kennedy Institute of RheumatologyMonoclonal antibodies
2000First clinical trials launched to test first immune checkpoint inhibitor drug containing a monoclonal antibody against CTLA-4 (ipilimumab, Yervoy®)AllisonMedarex, University of California BerkleyImmune checkpoint inhibitors, Immunology, Cancer immunotherapy, Oncology, Monoclonal antibodies
4 Oct 2000Michael Smith diedSmithUniversity of British ColumbiaGene editing, Genetics, Monoclonal antibodies
Mar 2002Cesar Milstein diedMilsteinLaboratory of Molecular BiologyAntibodies, Monoclonal antibodies, Immunology
Dec 2002First monoclonal antibody made using phage display approved for market CAT, BASF, AbbottMonoclonal antibodies, Phage display
5 Jan 2004Merrill W Chase diedChaseRockefeller UniversityAntibodies, Immunology
Apr 2004US FDA approved new imaging agent for detecting difficult to diagnose cases of appendicitis Wistar Institute, Palatin TechnologiesMonoclonal antibodies
11 Oct 2004David Murray died in La Garde-Freinet, FranceMurraySera-LabMonoclonal antibodies
May 2005Medarex and Ono Pharmaceuticals entered research alliance to develop a fully human anti-PD-1 antibody for the treatment of cancer Medarex, Ono PharmaceuticalImmune checkpoint inhibitors, Immunotherapy, Monoclonal antibodies
1 Jan 2006Hubert Schoemaker died in Philadelphia, USASchoemaker Monoclonal antibodies, Stem cells
Sep 2006First fully human monoclonal antibody drug approved Agensys, AmgenMonoclonal antibodies, transgenic
24 Nov 2008First anti-PD-1 antibody entered phase 1 clinical trial for cancer Medarex, Ono PharmaceuticalImmune checkpoint inhibitors, Immunotherapy, Monoclonal antibodies
4 May 2010Norman Klinman died in San Diego, California, USAKlinmanWistar Institute, University of PennsylvaniaAntibodies, Monoclonal antibodies, Immunology
25 Mar 2011First immune checkpoint inhibitor drug targeting CTLA4 (ipilimumab, Yervoy®), approved by the FDAAllisonMedarex, University of California BerkleyImmune checkpoint inhibitors, Cancer immunotherapy, Oncology, Monoclonal antibodies
17 Sep 2013European Commission approved Alemtuzumab (Lemtrada) for MS treatmentCompston, Coles, WaldmannCambridge University, SanofiMonoclonal antibodies, Campath
26 Oct 2013Michael Neuberger diedNeubergerLaboratory of Molecular BiologyMonoclonal antibodies, Transgenic animals
17 May 2014Gerald M Edelman diedEdelmanRockefeller UniversityAntibodies, Immunology

1997

FDA approved the first monoclonal antibody cancer drug for the American market

Dec 1997

First humanised monoclonal antibody approved for market

1998

FDA approved Trastuzumab (Herceptin) for the treatment of metastatic breast cancer

Aug 1998

FDA and European regulatory authorities approved the first monoclonal antibody drug for an autoimmune disease

2000

First clinical trials launched to test first immune checkpoint inhibitor drug containing a monoclonal antibody against CTLA-4 (ipilimumab, Yervoy®)

4 Oct 2000

Michael Smith died

Mar 2002

Cesar Milstein died

Dec 2002

First monoclonal antibody made using phage display approved for market

5 Jan 2004

Merrill W Chase died

Apr 2004

US FDA approved new imaging agent for detecting difficult to diagnose cases of appendicitis

11 Oct 2004

David Murray died in La Garde-Freinet, France

May 2005

Medarex and Ono Pharmaceuticals entered research alliance to develop a fully human anti-PD-1 antibody for the treatment of cancer

1 Jan 2006

Hubert Schoemaker died in Philadelphia, USA

Sep 2006

First fully human monoclonal antibody drug approved

24 Nov 2008

First anti-PD-1 antibody entered phase 1 clinical trial for cancer

4 May 2010

Norman Klinman died in San Diego, California, USA

25 Mar 2011

First immune checkpoint inhibitor drug targeting CTLA4 (ipilimumab, Yervoy®), approved by the FDA

17 Sep 2013

European Commission approved Alemtuzumab (Lemtrada) for MS treatment

26 Oct 2013

Michael Neuberger died

17 May 2014

Gerald M Edelman died