Superagonistic monoclonal antibodies: a novel and unique approach towards therapy of immunological diseases
Thomas Hanke
TeGenero
AG, Friedrich-Bergius-Ring 15, 97076 Würzburg
T lymphocytes play a key role
in initiating and terminating an immune response and are therefore attractive
targets for immunotherapeutic intervention both in situations of immunodeficiency
and autoimmunity. TeGenero has developed a unique approach to balance T cell
activation by triggering costimulatory receptors on T lymphocytes with a novel
class of “superagonistic” monoclonal antibodies (SuperMABâ). SuperMABâ with specificity
for CD28 induce well-tolerated activation and expansion of T cells in animals.
The observed lack of inflammatory side-effects relates to preferential activation
of regulatory T cells which are known to mediate peripheral tolerance and
suppression of autoimmunity. Accordingly, therapeutic potency of CD28-SuperMABâ could be shown
in animal models for autoimmune disease. It was mirrored by the in vitro
efficacy of CD28-SuperMABâ to stimulate human
regulatory T cells.
The recent identification of
the unique CD28-SuperMABâ epitope sets the
stage for the development of novel immunotherapeutics targeting CD28 and
related T lymphocyte receptors. TeGenero strives to develop innovative, highly
effective and broadly applicable immunotherapeutics to provide patients the
means to regain a functional and balanced immune system. Preparations to
achieve clinical proof-of-concept for CD28-SuperMABâ in conditions
of cancer-associated immunodeficiency and autoimmunity are under way.