Timeline

Learn more about the evolution of hybridoma technologies

1796

British country doctor Edward Jenner uses cowpox to inoculate patients and protect them against smallpox. Today, Jenner is recognized as the “Father of Immunology” for his contributions to the field of vaccination.

1890

Emil von Behring and Shibasaburo Kitasato show that serum from infected animals can be used to treat as well as prevent infection in other animals. Eventually their idea is carried out in humans and used to treat pediatric cases of diptheria.

1900

Paul Ehrlich introduces his side-chain theory: cells can express a variety of “side-chains” that can be released into the bloodstream and act as antitoxins or antikörpers (antibodies).

1914-1918

Horse serum therapy is expanded on a grand scale to combat tetanus during World War I; thousands of soldiers are presumed to have survived because of it.

1945

Following Karl Landsteiner’s discovery of the ABO blood group system as well as rhesus factors, Robin Coombs develops the Coombs test which detects pre-existing antibodies to rhesus factors in the blood.

1947

During the completion of her doctorate, Astrid Fagraeus demonstrates that plasma cells (mature B cells) are responsible for the production of antibodies.

1957

Frank Macfarlane Burnet proposes his clonal selection theory, explaining how lymphocytes respond in the presence of antigens and how each lymphocyte produces antibodies with a single specificity.

1965

After working with children suffering from Wiskott-Aldrich syndrome, Max Cooper and his collaborators discover the bursa of Fabricius (an organ exclusively found in birds) as the organ generating antibody producing B cells.

1969

Gerald Edelman describes the structure of an antibody protein.

1975

While working at Cambridge University, Georges Köhler and César Milstein concretize the idea of fusing myeloma cells with B cells, resulting in the creation of synkaryon cells, later named hybridomas, that have the capabilities of secreting antibodies of a single specificity.

1976

Susumu Tonegawa determines the rearrangement of immunoglobulin genes and demonstrates the genetic mechanism that results in antibody diversity.

1977

The Food and Drug Administration (FDA) approves first home pregnancy test which uses antibodies specific for the human chorionic gonadotropin (hCG) hormone.

1986

The FDA approves the first therapeutic monoclonal antibody: muromonab-CD3 for prevention of kidney transplant rejection.

1992

The FDA approves the first diagnostic monoclonal antibody: indium-111 satumomab pendetide, targeting the tumor-associated glycoprotein 72 (TAG-72), for the detection and imaging of colorectal and ovarian tumors.

1992-1995

James Allison and Tasuku Honjo independently discover the first cancer checkpoint inhibitors: programmed cell death-1 (PD-1) and cytotoxic T-lymphocyte-associated protein-4 (CTLA-4).

1998

The FDA approves the first cancer “immunotherapy”: trastazumab for human epidermal growth factor receptor (HER2) overexpressing breast cancer.

2006

The FDA approves the first fully human monoclonal antibody derived from a transgenic mouse: panitumumab for the treatment of epidermal growth factor-receptor (EGFR) positive colorectal cancer.

2020

Combined world-wide sales of monoclonal antibody-based therapies is estimated to reach $125 billion (Ecker, 2015)

Sources:

Ecker, D. M., Jones, S. D., & Levine, H. L. (2015). The therapeutic monoclonal antibody market. mAbs7(1), 9–14. doi:10.4161/19420862.2015.989042

Edward Jenner, Oil Painting
horse serum
side-chain theory
Robin Coombs
Bursa of Fabricus
Kohler and Milstein
Susumu Tonegawa
monoclonal antibody
James P Allison
Transgenic mouse
https://www.youtube.com/watch?v=43ngkc2Ejgw&list=PLGmxyVGSCDKvmLInHxJ9VdiwEb82Lxd2E&index=4

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