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

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

Nature nanotechnology (2020-12-16)
Xiao Huang, Jasper Z Williams, Ryan Chang, Zhongbo Li, Cassandra E Burnett, Rogelio Hernandez-Lopez, Initha Setiady, Eric Gai, David M Patterson, Wei Yu, Kole T Roybal, Wendell A Lim, Tejal A Desai

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, micrometre-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 tumour clearance while sparing uninjected tumours 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 substantially impact human primary T cell activation phenotypes. This modular and versatile biomaterial functionalization platform can provide new opportunities for immunotherapies.

Product Number
Product Description

Mowiol® 4-88, Mw ~31,000
Resomer® RG 504 H, Poly(D,L-lactide-co-glycolide), acid terminated, lactide:glycolide 50:50, Mw 38,000-54,000
Corning® cell strainer, pore size 40 μm, blue, sterile, pkg of (individually wrapped), pack of 50 ea
Tris(2-carboxyethyl)phosphine hydrochloride solution, 0.5 M, pH 7.0(aqueous solution; pH was adjusted with ammonium hydroxide)
CelLytic B Cell Lysis Reagent, For bacterial cell lysis, standard strength
Sucrose, ≥99.5% (GC)
Lipopolysaccharides from Escherichia coli O111:B4, γ-irradiated, BioXtra, suitable for cell culture
N-Acetyl-L-cysteine, suitable for cell culture, BioReagent
Penicillin-Streptomycin, Solution stabilized, with 10,000 units penicillin and 10 mg streptomycin/mL, 0.1 μm filtered, BioReagent, suitable for cell culture
Polylactic acid, Mw ~60,000
3-(2-Pyridyldithio)propionic acid N-hydroxysuccinimide ester, ≥95%, powder
Maleimide, 99%