Presently available cancer therapies are often not satisfactory. Application of cytostatics is associated with severe (long-term) detrimental side effects. Even the human monoclonal antibodies are not truly tumor specific and lead to side effects. In particular, there is a lack of effective therapies to prevent recurrence of the disease which is common due to the development of resistance to treatment as a result of target downregulation. These limitations are a consequence of the target choice.
Innovative therapies that allow for removal of the transformed cells while maintaining quality of life are therefore urgently required.
Since the inception of the company, it is our mission to serve patients with cancer by providing an efficacious specific treatment that preserves quality of life.
The targets to which APO-T directs its proprietary biologics belong to the cancer testis antigens, more specifically to members of Melanoma Antigen Gene Family A (MAGE-A).
Due to their intracellular expression MAGE-A proteins remain inaccessible targets for antibody-based therapeutics until they undergo proteasomal degradation into short peptides in the cytoplasm. These peptides are then transported into endoplasmic reticulum where they are loaded onto the Major Histocompatibility Complex Class-I (MHC-I molecules). In human MHC molecules are encoded on chromosome 6 by the gene complex called Human Leukocyte Antigen gene complex (HLA). Once located on the plasma membrane the peptide in complex with MHC-I is presented to the immune system. Molecules developed by APO-T share the intrinsic property of T-cell receptors in recognition of peptides presented in the context of MHC-I molecules.
Each MAGE-A protein is processed differently and results in presentation of different MAGE-A derived peptides in a particular MHC-I context. Furthermore, each MAGE-A protein presents different peptides when processed for a different MHC-I context. There are therefore different combinations within each MHC-I context and different combinations for each MAGE-A protein within one MHC-I context. The possible combinations are quite numerous, however, HLA distribution is quite unvaried in the human population and MAGE-A proteins are relatively conserved. The high homology between the twelve MAGE-A protein family members allows for identification of peptides that are shared by multiple family members. These multi-MAGE-A peptides are presented by MHC-I and thus allow multi-targeted therapy of tumors with heterogeneous expression of individual MAGE-A proteins in individual cells. APO-T considers this variation an asset since it provides the possibility of treating patients subsequently with different combinations, either targeting different MAGE-A peptides (in context of the same MHC-I molecule) or targeting MAGE-A peptides in context of different MHC-I molecules.
If you would like to learn more about our MHC-I/MAGE target please check out our review
The expression pattern of MAGE-A is restricted to germ cells of immune-privileged testis and placenta, as well as a wide range of malignant cells (but not on the surface of any of these cells). The only healthy cells that express MAGE-A proteins (of testis and placenta), do not express the MHC-I molecules. Cancer cells are therefore the only cells that express both MAGE-A and MHC-I molecules. Our antibody-based therapeutics are therefore truly tumor-specific as they specifically target intracellularly processed MAGE-A derived peptides once present on the cell membrane in complex with MHC class I molecules.
The expression of MAGE-A proteins in histologically different cancer types has been a subject of a number of studies. MAGE-A expression was shown in leading cancer types, including lung, breast, colon, prostate, pancreas and liver.
of our approach
Present day treatments target tumor cells but also kill normal cells. This is why treatments result in devastating effects on quality of life. At APO-T we are dedicated to develop drugs that do not kill normal cells. We have found a way to selectively kill cancer cells via a unique family of cancer cell markers. Normal cells do not have these markers. This creates the unique opportunity of treating cancer while maintaining quality of life.
In cancer every single treatment becomes less effective as over time the cancer builds up an evasive response. We exploit a family of markers to deal with the evasive response of the cancer cell by targeting different members of this family when resistance appears. This creates the unique opportunity of treating cancer for a prolonged period of time.
Due to our choice of tumor target, MHC-I/MAGE-A complexes, our proprietary antibody-based therapeutics offer unprecedented advantages, such as:
- Broad applicability across different tumor indications
- Explicit tumor specificity
- Opportunity for treatment continuation when escape occurs