Fragments of all cellular proteins are exposed on the cell surface by so-called MHC-1 proteins to the immune system. APO-T has developed proprietary molecules that are capable of targeting any tumor cell that expresses a specific MAGE-A peptide in the context of the MHC-1 complex (MAGE-MHC-1 peptide complex).
Targeting of MHC-peptide complexes on the surface of tumor cells represents an attractive therapeutic option based on:
Tumor specificity. MHC-associated MAGE-A peptides are uniquely exposed by tumor cells derived from a variety of tissues.
Prevention of escape. Tumor cells potentially down-regulate MAGE-A expression to escape AIM treatment. However, MAGE-A expression appears necessary for a tumor cell to avoid apoptosis, since gene-silencing of MAGE-A results in apoptosis. MAGE down-regulation by a tumor cell may therefore be an unlikely mechanism of escape of the cell.
Alternating treatment. In the event a tumor down-regulates the MAGE-MHC-1 peptide complex recognized by AIM-1, AIM-2 specific for another MAGE-MHC-1 peptide complex (e.g. targeting HLA CW7 instead of HLA A0201 of the MHC molecule) may be used to continue treatment. Every patient (co-) presents at least three different targets for AIM therapy.