DNA scaffolds enable efficient and tunable functionalization of biomaterials for immune cell modulation

Huang, Xiao, University of California, San Francisco, https://orcid.org/0000-0001-7733-9094

Williams, Jasper Z., University of California, San Francisco

Chang, Ryan, University of California, San Francisco

Li, Zhongbo, University of California, San Francisco

Burnett, Cassandra E., University of California, San Francisco

Hernandez-Lopez, Rogelio, University of California, San Francisco

Setiady, Initha, University of California, San Francisco

Gai, Eric, University of California, San Francisco

Patterson, David M., University of California, San Francisco

Yu, Wei, University of California, San Francisco

Roybal, Kole T., University of California, San Francisco

Lim, Wendell A., University of California, San Francisco

Desai, Tejal A., University of California, San Francisco

xiao.huang2@ucsf.edu

Published Oct 16, 2020 on Dryad. https://doi.org/10.7272/Q6CC0XXJ

Cite this dataset

Huang, Xiao et al. (2020). DNA scaffolds enable efficient and tunable functionalization of biomaterials for immune cell modulation [Dataset]. Dryad. https://doi.org/10.7272/Q6CC0XXJ

Abstract

Biomaterials can improve the safety and presentation of therapeutic agents for effective immunotherapy, and a high level of control over surface functionalization is essential for immune cell modulation. Here, we developed biocompatible immune cell engaging particles (ICEp) that use synthetic short DNA as scaffolds for efficient and tunable protein loading. To improve the safety of chimeric antigen receptor (CAR) T cell therapies, micron-sized ICEp were injected intratumorally to present a priming signal for systemically administered AND-gate CAR-T cells. Locally retained ICEp presenting a high density of priming antigens activated CAR-T cells, driving local tumor clearance while sparing uninjected tumors in immunodeficient mice. The ratiometric control of costimulatory ligands (anti-CD3 and anti-CD28 antibodies) and the surface presentation of a cytokine (IL-2) on ICEp were shown to significantly impact human primary T cell activation phenotypes. This modular and versatile biomaterial functionalization platform can provide new opportunities for immunotherapies.

Funding

National Cancer Institute, Award: 1U54CA244438