Abstract
The immunosuppressive nature of cancer prevents a sustained response to T-cell-inducing vaccines. We hypothesize that co-delivering antigens and adjuvants directly to sub-compartments of antigen presenting cells could elicit specific CTL and Th1 activation, providing more control over the immune response. To accomplish this goal, we are developing protein nanoparticles capable of delivering payloads consisting of RNA, protein, and small molecules to target cells. One class of protein nanoparticles is produced in E. coli and is capable of packaging its own RNA to enable evolution of improved functions such as increased RNA packaging, improved serum stability, and pH-mediated disassembly for endosomal payload delivery. Another class of protein nanoparticles can bud from HEK293F cells containing small molecule adjuvants and mRNA-encoded antigens. By pseudotyping these enveloped protein nanoparticles with viral fusion proteins, we can deliver nucleic acids to the cytosol of target cells where they are translated to produce the desired protein antigen. These non-viral delivery devices could improve our ability to control immune responses against cancer.
Citation Format: Marc J. Lajoie, Gabriel Butterfield, Elizabeth Gray, Kate DaPron, Daniel Stetson, David Baker, Neil King. Protein nanoparticles for controllable T cell activation [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr B073.
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