678P - ExoDS: A bioengineered exosome-based capsule for targeted delivery of chemotherapy drugs to cancer cells and cancer stem cells

Background

Cancer stem cells (CSCs) are the major cause of therapy failure. CSCs are responsible for cancer relapse, metastasis, chemo-resistance, and radiation resistance. Therefore, targeting CSCs is imperative for better therapy outcomes. To date, there is no therapy precisely targeting CSCs. To fill these lacunae we have developed ExoDS a bioengineered exosome-based platform to precisely deliver chemotherapy drugs directly to CSCs effectively eliminating them.

Methods

ExoDS is an exosome-based platform that has been isolated and purified from immune cells that have been treated with a patented bioformulation and the specific drug to be incorporated within exosomes. To test the efficacy of ExoDS in targeting CSCs, we first generated and isolated CSCs from breast cancer cell lines, MCF7, MDA-MB-231, and MDA-MB-468. We next isolated CSCs from chemo-naïve breast tumor tissue samples to test the efficacy of ExoDS in targeting breast CSCs. We extensively used flow cytometric dependent analysis of AnnexinV to determine apoptosis in CSCs.

Results

Our results have shown that ExoDS can specifically identify and target CSCs with a 12-fold higher efficiency as compared to free drugs. At a cellular level, we established that ExoDS gets internalized inside CSCs within 6hrs of treatment. ExoDS was also found to target CTCs isolated from patient blood (n=5). Further analysis revealed that ExoDS spared healthy PBMCs isolated from healthy donors (n=9) as well as breast cancer patients (n=7). Our data confirmed that ExoDS can reduce chemotoxicity by more than 30%. Broadly, our results highlight the benefits of using ExoDS as compared to free chemotherapy drugs. ExoDS is a potential chemotherapy alternative.

Conclusions

Collectively, ExoDS efficiently targeted CSC in-vitro and also ex-vivo. Its specificity towards CSCs was established by the inability of ExoDS to target PBMCs derived from healthy individuals as well as patients. ExoDS can potentially target CSCs in a clinical setting making it a first-of-its-kind therapy vehicle. Targeting CSCs will revolutionize cancer treatments and will lead to better therapy outcomes. Currently, we are testing ExoDS in murine models to test it's in vivo efficacy and efficiency.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Exsure.

Funding

Biotechnology Industry Research Assistance Council (BIRAC), Government of India.

Disclosure

A. Dutta, S. Paul, S. Bhagat: Financial Interests, Institutional, Full or part-time Employment: Exsure.