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My name is Herman Waldmann from the Dunn School of Pathology of Oxford University.
I'm going to be discussing the immunogenicity problem in antibody therapy.
As many of you will know,
antibodies have become widely used in recent years against
a whole range of human disorders.
For many patients, this has provided good treatments.
But where treatment is needed long-term,
antibody immunogenicity from foreigners has been a real dilemma,
limiting the usage time under pharmacokinetics of the therapeutic agent.
This talk will be about trying to
eliminate this immunogenicity of therapeutic antibodies.
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What are the features of antibodies that result in
them eliciting neutralizing antibody responses to themselves?
Well, first of all, their sequences will be different to that of the patient.
We think of that and talk about that as foreignness.
That foreignness would result in two things.
It would result in the stimulation of
helper T cells seeing distinct peptides or epitopes,
and being immunized as a result.
Once the helper cells are immunized,
they would help B lymphocytes to make
antibody responses against the therapeutic proteins.
In order to be seen by helper cells and to immunize them,
proteins need to be degraded.
That's sometimes referred to as antigen processing,
and it is conducted by its very specialized macrophage-like cells called dendritic cells.
That though isn't enough,
the recognition of foreignness is not enough.
There has to be, at the same time,
the generation of innate immune or what is called dangerous signals,
often associated with inflammation, release of cytokines,
generation of compliment components, or cell-cell simulation.
Finally, aggregates and cell binding giving cell
surface artificial aggregates do create a bias towards immunogenicity.
