Engineering cell-cell interactions has proven to be quite valuable due to the vast number of therapeutic applications that benefit from this technology. Although genetically engineering artificial receptors onto a patient’s cells has shown some success, preparation is costly, current applications are limited, and modifications are permanent. To address some of these concerns our lab has developed a non-genetic approach to facilitate selective cell-cell interactions using various targeted protein scaffolds. To date, we have employed commonly used targeting elements such as short peptides and single chain variable fragments (scfv), and alternative binding scaffolds such as affibodies and fibronectins that are engineered to have specificity for overexpressed cancer antigens. The diversity of the CSAN construct can be expanded by fusing two scaffolds onto the same ring that target different cellular antigens, creating a bispecific nanoring. Our lab has shown that functionalizing the CSAN construct with a cancer antigen-targeting scaffold and a T-cell targeting single chain antibody fragment (anti-CD3 scfv) forms a stochastic mixture of bispecific nanorings with the ability to traffic T-cells to the tumor. We are currently able to produce CSANs that facilitate T-cell interactions with: a) solid tumor antigens such as EpCAM, EGFR, etc. b) blood tumor antigens such as CD19, CD22, etc. c) cancer-initiating cell associated antigens such as CD133 and B7H3. Our rings have been shown to be stable in vitro and in vivo and can be used to deliver drugs or nucleic acids as well as for fluorescence and PET imaging. Finally, a distinct advantage of our construct over other bispecific immunotherapies is that we are able to disassemble our rings using the FDA approved drug trimethoprim, stopping the course of treatment.

Development of targeted chemically self-assembling nanorings (CSANs) for cell-directed immunotherapy

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.