Multifunctional fusion proteins for cancer immunotherapy
Modulation of immune system by simultaneous blocking and activation of signaling pathways can lead to the synergistic effect in cancer immunotherapy. Recepton is developing a technology platform for generation of biological drugs targeting inhibitory and stimulatory pathways of the immune system. The drug development platform includes:
- Rational design of multifunctional fusion proteins
- Generation of genetic constructs
- CHO cell line construction
- Bioprocess development
- Protein purification
- Protein characterisation
- Cell based assays
- Studies in animal models
Figure 1. Immnune checkpoint receptors and their ligands.
Signaling pathways that modulate T-cell functions
| Ligands | Receptors | Role |
|---|---|---|
| B7 receptor family | ||
| PD-L1 (B7-H1, CD274) | PD-1 (CD279) | Inhibition |
| CD80 (B7-1) | Inhibition | |
| PD-L2 (B7-DC, CD273) | PD-1 (CD279) | Inhibition |
| ICOSL (B7-H2, CD275) | ICOS (CD278) | Activation |
| CD28 | Activation | |
| CD276 (B7-H3) | Unknown receptor | Inhibition |
| VTCN1 (B7-H4) | Unknown receptor | Inhibition |
| VISTA (B7-H5) | Unknown receptor | Inhibition |
| HHLA2 (B7-H7) | TMIGD2 (CD28H) | Activation |
| CD80 (B7-1) | CD28 | Activation |
| CTLA-4 | Inhibition | |
| B7-H1 | Inhibition | |
| CD86 (B7-2) | CD28 | Activation |
| CTLA-4 | Inhibition | |
| lg superfamily | ||
|---|---|---|
| MHC-II | LAG-3 (CD223) | Inhibition |
| Gal-9 | TIM-3 | Inhibition |
| PVR (CD155) | TIGIT | Inhibition |
| HVEM (CD270) | BTLA (CD272) | Inhibition |
| CD160 | Inhibition | |
| LIGHT | Activation | |
| TNF receptor family | ||
|---|---|---|
| OX40L (CD252) | OX40 (CD134) | Activation |
| GITRL | GITR (CD357) | Activation |
| 4-1BBL | 4-1BB (CD137) | Activation |
| CD70 | CD27 | Activation |
| CD40L (CD154) | CD40 | Activation |