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I am Andre Frenzel, currently CSO of
YUMAB GMBH which deals with Phage Display Technology,
and this is also the topic of the talk of today,
which is Phage Display for the Generation of Monoclonal Antibodies,
better human antibody discovery and development by in vitro selection.
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The history of recombinant antibodies began in 1975,
when Kohler and Milstein published their groundbreaking work about Hybridoma technology.
They were awarded in 1984 with the
Nobel Prize in Physiology and Medicine for
their work on the immune system and the production of monoclonal antibodies.
The Nobel Prize has also been awarded to Jerne,
who's very often forgotten in this respect,
but he also had a quite impact about topics of the immune system;
you already recognized that the immune system
contained antibodies prior to the antigen contact,
yet had some nice ideas about self-tolerance and
also found out that there is a communication between B and T cells.
So, there's really groundbreaking work in the immunology field.
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The first therapeutic antibody competed on the market in 1985,
OKT3 (Muronomab) marketed by Jannsen-Cilag.
This is, of course, an Hybridoma-derived antibody against CD3,
for the therapy of acute with the different resistance-
a rejection of allogenic renal heart and liver transplants.
The mode of action is that upon binding of Muronomab to the cell surface receptor,
ADCC and CDC occurs that leads to T-cell depletion,
but it has also be mentioned that OKT3 has
also very severe side effects such as T-cell activation,
which might lead to a cytokine storm.
OKT3 led to an anti-mouse response of
38-83 percent in patients who were treated with this antibody,
and therefore, OKT3 was discontinued in 2010.