Focus and vision define the path to a successful cancer drug
Aminex Therapeutics’ primary focus is developing drugs for immuno-oncology therapy. Its lead drug, a novel immune suppressor cell modulator therapy, AMXT 1501/DFMO, has advanced to the late preclinical stage. To help you understand the AMXT 1501/DFMO approach, here is a brief introduction to some of the terms used.
Myeloid-derived suppressor cells (MDSCs) are non-differentiated immature stem cells derived from bone marrow. MDSCs are found in increased quantities in tumor microenvironments, and they suppress the immune system’s response to cancer. Polyamines are found in every cell in the body and are required for cell growth and division. Polyamines are used by cancer cells as suppressors to avoid detection and attack by the immune system. Ornithine is the starting point for the synthesis of polyamines, which are produced in increased quantities by cancer cells, principally driven by the MYC oncogene.
Polyamines contribute to an increase of MDSCs in cancer microenvironments. Increased polyamines and MDSCs are major suppressors of the immune system’s response against cancer. Suppressor cell modulators such as AMXT 1501/DFMO work by reducing these suppressive brakes on the immune system, helping it to attack cancer cells and their metastases. MYC and RAS, two primary oncogenes, promote the development of multiple cancers that have been efficaciously treated by AMXT 1501/DFMO in multiple animal cancer model tests.
Therapeutic approaches to inhibit cancers’ resistance to immune mechanisms are among the most promising drugs undergoing development today. Elevated tumor and tumor microenvironment concentrations of polyamines and MDSCs are associated with accelerated tumor growth and suppression of an immune response to those tumors. AMXT 1501/DFMO directly reduces these elevated concentrations of MDSCs and polyamines to the extent that the body’s own immune system is enabled to attack the cancer cells.
Cancer cells have evolved sophisticated survival mechanisms to suppress tumor-specific immune responses (immunosuppression). Part of such an “immune-editing” process involves the establishment of an immunosuppressive tumor microenvironment. This is a major cause for the failure of anticancer treatment regimens historically tested in clinical trials. AMXT 1501/DFMO has been developed as an immunomodulatory mechanism (modulating or regulating immune functions) to be effective not only against primary tumors, but also against their recurrence and metastases. Aminex animal tests have confirmed that AMXT 1501/DFMO activates the innate immune system, and enables the adaptive immune system's “memory” to provide long-term resistance to the cancer.