10.7272/Q6CC0XXJ
Huang, Xiao
0000-0001-7733-9094
University of California, San Francisco
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
DNA scaffolds enable efficient and tunable functionalization of
biomaterials for immune cell modulation
Dryad
dataset
2020
National Cancer Institute
https://ror.org/040gcmg81
1U54CA244438
2020-10-16T00:00:00Z
2020-10-16T00:00:00Z
en
https://doi.org/10.1101/587105
42032993 bytes
4
CC0 1.0 Universal (CC0 1.0) Public Domain Dedication
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.