Monoclonal antibodies

Monoclonal antibody therapy

Recombinant antibody engineering

  • antibody production by the use of viruses or yeast, rather than mice.

Examples (of many)

  • Casirivimab/imdevimab (REGEN-COV): MAB against SARS-CoV-2 spike protein

  • Infliximab/adalimumab: bind and inhibit TNF-⍺ (effective in RA, Crohns, UC)

  • Ramucirumab: against malignant cells (cancer, e.g. lymphoma)

  • Tocilizumab/Sarilumab: MAP against IL-6 cytokine receptor (IL-6 inhibitor)

  • Basilizimab/daclizumab: inhibit IL-2 on activated T cells (prevent kidney tx rejection)

  • Omalizumab: inhibits IgE (athma)

History

  • In the early 1900s, immunologist Paul Ehrlich proposed the idea of a Zauberkugel – "magic bullet", conceived of as a compound which selectively targeted a disease-causing organism, and could deliver a toxin for that organism. This underpinned the concept of monoclonal antibodies and monoclonal drug conjugates. Ehrlich and Élie Metchnikoff received the 1908 Nobel Prize for Physiology or Medicine for providing the theoretical basis for immunology.

  • By the 1970s, lymphocytes producing a single antibody were known, in the form of multiple myeloma – a cancer affecting B-cells. These abnormal antibodies or paraproteins were used to study the structure of antibodies, but it was not yet possible to produce identical antibodies specific to a given antigen. In 1973, Jerrold Schwaber described the production of monoclonal antibodies using human–mouse hybrid cells. In 1975, Georges Köhler and César Milstein succeeded in making fusions of myeloma cell lines with B cells to create hybridomas that could produce antibodies, specific to known antigens and that were immortalized. They and Niels Kaj Jerne shared the Nobel Prize in Physiology or Medicine in 1984 for the discovery.

  • In 1988, Greg Winter and his team pioneered the techniques to humanize monoclonal antibodies, eliminating the reactions that many monoclonal antibodies caused in some patients. By the 1990s research was making progress in using monoclonal antibodies therapeutically, and in 2018, James P. Allison and Tasuku Honjo received the Nobel Prize in Physiology or Medicine for their discovery of cancer therapy by inhibition of negative immune regulation, using monoclonal antibodies that prevent inhibitory linkages.

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