Collection: Checkpoint Proteins

At the core of the checkpoint immuno-onco-therapy is the infiltrated T-lymphocytes expressing an array of checkpoint proteins on the cell surface for proximal interrogation of the tumor microenvironment. The temporal and kinetic engagement of one or more of these receptors with the respective ligand(s) lead to an overall activating or inhibitory state of these T cell and result in suppressing or facilitating the growth tumor cells, respectively.

At the core of the checkpoint immuno-onco-therapy is the infiltrated T-lymphocytes expressing an array of checkpoint proteins on the cell surface for proximal interrogation of the tumor microenvironment. The temporal and kinetic engagement of one or more of these receptors with the respective ligand(s) lead to an overall activating or inhibitory state of these T cell and result in suppressing or facilitating the growth tumor cells, respectively.

The revelation of the bi-directional signaling capacities of the B7/CD28 proteins blurs the line between ligand and receptor of this family proteins. Though all receptors interact with the ligands within the structurally related Ig superfamily (IgSF), except for BTLA which interacts with both B7-H4 and HVEM, the latter being a member of the TNF receptor superfamily (TNFRSF). The functional studies on B7/CD28 superfamily proteins have shown that they not only promote the initial T cell activation, but also regulate the self-tolerance by supporting CD4+CD25+Treg for the homeostasis. Importantly, CTLA-4 exerts the inhibitory effects via both B7-1/B7-2 dependent and independent fashions. The newer members of the B7 family, ICOSL, PD-L1, PD-L2, B7-H3, and B7-H4 can express on both professional APCs and cells of non-lymphoid organs, hence, providing novel mechanism for regulating T cell activation and tolerance in peripheral tissues. ICOS/ICOSL and B7-1/B7-2 pathways are synergistic for promoting T-dependent antibody responses, yet ICOS/ICOSL axis only stimulates the T cell effector function but not T cell expansion. Engagement of PD-1 with its ligand (PD-L1 and PD-L2) triggers inhibitory signals, diminishes cell proliferation and cytokine production. The PD-1/PDL1/PDL2 axis is widely regarded to play critical roles in failed antitumor immunity and are therefore under rigor investigations for developing oncological therapeutics.

Our B7/CD28 Ig-Fc fusion proteins are homodimers linked by a pair of disulfide bonds at the hinge region of mouse IgG2a, affinity purified and size-excluded to homogeneity