Novel molecules to generate ICP inhibitors
VHH molecules are derived from immunoglobulins expressed by certain species of camelids (notably Alpacas). These are shorter, single-domain versions of their larger antibody counterparts. These molecules are around 10 times smaller than common antibodies, but they retain equivalent selectivity and affinities.
While they lose certain properties of regular antibodies, such as the ability to trigger an immune response through the Fc fragment, the small size of VHH allows far greater permeability in tissues, as well as the ability to bind to hard-to-access areas of antigens which large antibodies could not reach. Additionally, VHH do not trigger inflammatory reactions as antibodies tend to do.
The IVS-5001 nanobody
As part of its HLA-G platform, Invectys is developing a VHH designed to prevent ILT4 inhibitory receptor binding HLA-G and other ligands. ILT4 is normally expressed on Antigen Presenting Cells (DC, Monocytes, macrophages) and is strongly upregulated on tumor-associated macrophages (TAM), tumor-associated neutrophils (TAN) and on myeloid-derived suppressor cells (MDSC), key elements of the immuno-suppressive micro-environment.
Strikingly, although ILT4 is an inhibitory immune receptor, it can also be neo-expressed on tumors, enabling greater proliferation and dissemination capabilities upon interaction with HLA-G or ANGPTL-2 pro tumoral proteins.
IVS-5001 is a first in class VHH specific to the ILT4 inhibitory receptor, demonstrated to block not only ILT4’s interaction with HLA-G but also with ANGPTL-2. This VHH could potentially reprogram immuno-suppressive microenvironment, to restore anti-tumoral activity.
This VHH is currently in pre-clinical studies.
A glossary is available for technical definitions.
