Exclusively licensing our Research and Intellectual Property from the University of California Davis Cancer Center.
Our therapeutic drug consists of two peptides: Transformable Peptide Monomers (“TPM”) 1 and TPM 2, that contain molecules targeting Cancer; and molecules that aggregate the peptides together to form a nanoparticle.
Key Domains:
- KLVFF: Responsible to aggregate the peptides together to form a nanoparticle
- R848: Resiquimod is a potent immuno-stimulant
- LLP2A: Ligand to capture the immune cells
- LXY30: Ligand that targets the α3β1 integrin heterodimeric transmembrane receptor expressed by many epithelial tumors with high metastatic potential
- Under aqueous conditions and in blood circulation, TPM 1 and TPM 2, at a ratio of 1:1, will co-self-assemble into nanoparticles.
- Nanoparticles would preferentially accumulate in tumors through the leaky tumor vasculatures.
- Upon interaction with α3β1 integrin receptor protein displayed on the tumor cell membrane, the nanoparticles would undergo transformation into nanofibers forming a nanofibrillar structural network on the surface of tumor cells, thus maintaining a prolonged retention.
- Nanofibrils are important for prolonged retention in the tumor microenvironment.
The graphic depicts the processes for how a programmable bispecific Nano Immuno-Engager synergizes Immune Checkpoint Blockade therapy in the tumor tissue:
- (I) NIE-NPs bind tumor cells and in situ transforms them into nanofibrils (NIE-NFs) on the surface of tumor cells.
- (II) NIE-NFs expose LLP2A and release R848
- (III) for capturing T cells to tumors cells
- (IV) re-educating TAMs from M2 to M1 phenotype
- (V) Meanwhile, anti-PD-1 antibody greatly activates the NIE homed cytotoxic T cells for ICB therapy.
- The sustained release of R848 from the nanofibrillar network would improve the immunosuppressive tumor microenvironment, e.g., activate antigen-presenting cells, promote immune cells to produce antitumor response factors, and re-educate the phenotype of the macrophage from M2 to M1.
- This in vivo structural transformation-based supramolecular bispecific NIE represents an innovative class of programmable receptor-mediated targeted immunotherapeutics against cancers through capturing of T cells and enhancement of the antitumor immune state at the TME.
