EOS-448 blocks the TIGIT receptor, enhancing anti-tumor activity, and the death of tumor cells further augments the immune response.
1) EOS-448 binds to TIGIT, leaving the CD226 receptor free to bind to CD155 and CD112 without competition. This blocks activation of TIGIT’s immunosuppressive function and activates anti-tumor immune cells.
2) Tumor destruction can lead to cross presentation of antigens by Antigen Presenting Cells (APCs) to T cells and augmentation of the immune response.
This figure illustrates the mechanisms by which EOS-448 a anti-Tigit antibody mediates a immune activation that leads to two tumor cell killing. The figure is divided into two panels.
Panels 1 labeled on the left is a diagram that illustrates the first mechanism of action of EOS-488
Two spheres with draw side by side.
The sphere on the left represents a tumor cell and the other sphere an immmune cell labelled here as T cell or a NK cell.
A thickly draw boarder on each sphere represents the cell membranes.
Rooted in membrane and bridging the gap between the two cells are a pair of objects that form a ball and socket joint with the opposite cell. The objects represent the ligand and receptor interaction between the Tumor and the Immune cell respectively. On the tumor cell the two ligands are labelled CD112 on upper right and CD155 on the lower right. On the T cell corresponding receptors are labelled TIGIT on the top left and CD226 on the bottom left. A “Y” shaped structure draw on its side with the upper part of the Y facing TIGIT, interrupts the potential ball and socket joint made by CD112 and TIGIT, represents EOS-488 the anti-TIGiT antibody. A dotted arrow shaped like an upside arc that points from CD155 on the lower side of the sphere, into the T cell illustrates that this interruption by EOS-488, allows transmission of a immune activation signal via the interaction of CD155 and CD226. Finally a dotted arrow drawn arching from the top side of the T cell pointing to the Tumor cells illustrates that together the disruption leads to Tumor cell killing.
The results of tumor cell killing is illustrated in Panels 2 labelled 2, on the right on the figure.
Drawn in a vertical row are three cells. The top a dying Tumor cell is depicted as a sphere with an irregular boarder and small irregular shaped object randomly dispersed around it. The latter represent tumor particles or antigens that are released when a tumor cell dies. Below the Tumor cells is an antigen presenting cell depicted as a sphere with rounded spikes protruding from the perimeter, known as dendrites or pseudopodia. A arching arrow on the left from the Tumor cell down to the APC, indicates that the tumor antigen is captured by APC, in addition draw as tumor antigens on the tips of the dendrites of the APC. A second arrow on the left of the cells points from the APC to a third smooth sphere below indicates that APC intern activates T cells and leads to Tumor Specific Tcell