Aethlon Medical, Inc. — Department of Health and Human Services SBIR Phase I: 100

Description

ABSTRACT An overarching challenge in breast cancer oncology is the urgency to revolutionize treatment regimens by replacing them with ones that are more effectiveless toxicand improve the rates of survivalRecent years have seen exponential interest in tumor derived exosomesnano sizednmvesicles shed in large quantities by tumor cells and laden with oncogenic cargo from their parent tumor cellResearch studies have shown that breast cancer cells produce copious quantities of exosomes that are released systemically and mediate tumorassociated immune suppressionresistance to therapiestissue invasionand metastasisBreast cancer exosomes express oncoproteins on their surfaces that have been shown to exert direct actions in interfering with the activity of therapeutic monoclonal antibodiesand countering chemotherapeutic agentsThese lines of evidence strongly support the development of strategies to limit the effects of tumor derived exosomeshoweverno such targeted therapeutic strategy existsThe proposed research entails an ex vivo evaluation of a medical devicethe Hemopurifieras a strategy for the capture and removal of exosomes from the plasma of breast cancer patientsThe clinical grade Hemopurifier comprises an extracorporeal hemodialysis cartridge containing a lectinGalanthus nivalis agglutininGNAaffinity matrixAethlon has successfully completed an FDA approved feasibility study using the Hemopurifier for addressing infectious viruseswhich have similar sizes and glycosylation signatures as cancer exosomesAethlon has also received an Expedited Access PathwayEAPdesignation from the FDA to support the advancement of the Hemopurifier to treat life threatening virusesFor this prospective new indication for use of the deviceour central hypothesis is that the Hemopurifier can be used to target breast cancer exosomes by capturing and removing these vesicles from plasmaIn this studyexosomes originating from triple negative and HERoverexpressing breast cancer cells will be used as a model since research studies have defined the functions of these vesicles in immunosuppression and promoting tumor growthThe proposed proof of concept studies will provide insight into whether exosomes targeted by the Hemopurifier possess signatures and functions that are disease relevantWe envision that an extracorporeal approach for removing disease mediating exosomes from circulation may replace or reduce the need for toxic drugs or unmask their efficacyconceivably serving as an adjunct to standard of care breast cancer treatments NARRATIVE Despite the abundant support from research studies for oncogenic roles of tumor derived exosomesa therapeutic strategy for addressing these nanovesicles has not been devisedThe proposed research entails an ex vivo evaluation of a medical devicethe Hemopurifieras a strategy for removal of breast cancer exosomes from circulating bloodThe Hemopurifier comprises an extracorporeal hemodialysis cartridge containing a lectin affinity matrixThis device has been applied successfully in an FDA approved study for addressing infectious viruses having similar sizes and glycosylation signatures as cancer exosomes