The MAGE-A antigen is a cancer testis antigen that is expressed within the human testes. It is highly immunogenic and has been considered as a viable target for the development of immunotherapies of tumors overexpressing the MAGE-A family of antigens. The MAGE-A sub-family of cancer testis antigen is expressed in germ cells, though not exclusively. They may drive malignancy and since those antigens are highly immunogenic they lend themselves to possibly becoming potential effective target for immunotherapies. Antigens particular to each MAGE-A family, has a unique expression pattern and related tissue target, which defines its differential use as immunotherapy regiments.
The present application claims benefit from the data, which identifies MHC Class I and MHC Class II specific restricted epitopes that are immunogenic. Restricted epitopes can be used in the development of immunotherapies targeting tumors that expresses MAGE-A family of tumors.
The restricted peptides will be part of an immunotherapy construct that could be used for the treatment of many tumors, with specific targets being Triple Negative Breast Cancer (TNBC). The immunotherapy will take advantage of differential expression of MAGE protein variants via the MHC Class I pathway for T-Cell CD8+ lymphocytes, which will be complemented by the production of antibodies from B-cells via CD4+ lymphocytes.
Delivery Technology: SMARTmid™ vectors
SMARTmid™ vectors (licensed from PepVax, Inc.) has been designed to be a DNA-based delivery system that can directly enhance the immune system via CD8+ and CD4+ lymphocytes that will then lead to tumor load reductions or the prevention of tumor recurrence. Pre-clinical studies of SMARTmid™ vectors along with anti-PD-L1 and/or anti-CTL4 is undergoing testing to demonstrate the potential to initiate a systemic immune response that can be lead decrease toxicities of current chemotherapies. In addition, SMARTmid™ vectors in conjunction with anti-PD-L1 and/or anti-CTL4 can be used as a standalone treatment for many tumors that express the protein antigens, like MAGE A. Through prior studies, specific regions of viral proteins, such as, the lentiviral integrase protein, is capable of enhancing nuclear transport of viral DNA. The second-generation SMARTmid™ vectors will incorporate portions of such viral proteins that can by themselves enhance viral DNA import into the nucleus. The DNA localization properties of the SMARTmid™ vectors DNA elements are magnified when used in combination with viral proteins added exogenously. The fully synthetic method for producing lentivirus-like vector particles for mammalian cell transduction is a powerful template in which to build an immunotherapy for the treatment of MAGE-A antigen expressing tumors.