Figure 1. Di-block HPMA polymeric platform delivery of KT-1 (polymeric epirubicin) and MPPA (multivalent polymeric PD-L1 peptide antagonist) have optimized the immunotherapeutic approach to solid tumors.
Figure 2. Platform delivery of epirubicin results in the lysosomal cleavage of epirubicin which then intercalates into the DNA within the nucleus. This causes a highly immunogenic cell death that releases multiple antigens that can be recognized by the immune system.
Figure 3. The diverse antigen exposure created by the highly immunogenic epirubicin creates a durable immune response and converts immunologically cold tumors into hot tumors.
Figure 4. Tumor cells can survive when they express the ligand PD-L1. They can inactivate the immune cells’ ability to kill them through PD-L1/PD-1 checkpoint interactions. This checkpoint interaction allows the tumor to grow further by evading the immune system. MPPA causes multivalent PD-L1/PD-1 checkpoint inhibition that allows the immune system to again recognize and kill tumor cells. MPPA reactivates this robust immune surveillance.
Figure 5. In addition to checkpoint inhibition, MPPA, causes a clustering and destruction of the PD-L1 ligand on the tumor cells resulting in the dramatic reduction of PD-L1 recycling to the cell surface, a first in class action. This action further enhances the immune system’s recognition of tumor cells and their destruction resulting in improved survival rates for solid tumors.
Figure 6. Testing in a variety of preclinical solid tumor models (breast, colon, lung, ovarian, and pancreatic) have shown complete responses, long term survivals and a dramatic reduction in adverse effects. We are now planning Phase 1, Investigational New Drug (IND) testing which documents safety and initial dosing parameters for human use.