De novo Biotherapeutics is developing multi-specific antibodies via mRNA technology to harness the anti-tumor activity of patients’ own
NK cells and will be the first mover for mRNA-based NK engager development. The three pillars of De novo Biotherapeutics’ strategy are as follows:
Immune
Cell-engaging Antibody
Immune cell-engaging antibody, so called immune cell engager,
is a quite versatile technology that could be engineered with the goal
of delivering therapies that direct patients’ own immune cells to tumor cells,
activating their cytotoxic potential. This new format of antibody is designed
to redirect NK cells to cancer cells leading the formation of a cytolytic synapse,
triggering NK cell activation and the release of cytolytic granules, such as
perforin and granzyme.
Natural Killer Cells
Natural killer cells, also known as NK cells, are type of
cytotoxic lymphocyte critical to the innate immune system
having cytotoxic functions mediated by release of
cytotoxic granules and Fas ligand and also produce cytokines.
The role of NK cells is analogous to that of cytotoxic T cells,
which are able to recognize and kill cancer cells,
however, they are likely to be safer than T-cell-involved treatments.
NK cell-based immunotherapies may be less likely to cause
cytokine release syndrome and neurotoxicity because the spectrum
of cytokines produced by these cells is different from that
secreted by T cells and associated with these adverse events
mRNA/Lipid Nanoparticle
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In order to develop next-generation drug products that
allow multiple functionalities, increasing both efficacy and
safety, there have been many approaches such as bi- or
multi-specific antibodies. However, although there are
many benefits of multi-specific antibodies, in the light of
complexity of designing and creating these modalities,
there are also many challenges in manufacturing both
from an expression and a process point of view. -
These include low titers, variability in product quality,
impurities, aggregation and poor stability resulting in extremely
expensive drug price. In order to overcome these protein-based
manufacturing issues, De novo Biotherapeutics aims to develop
bi-, multi-specific modality via mRNA/lipid nanoparticle technology
which has many advantages over protein-based therapeutics.