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

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.

Tight nanoscale clustering of Fcγ-receptors using DNA origami promotes phagocytosis

“…These results suggest that oligomerization may lead to more effective therapy; however, a systematic study of the spatial parameters that affect FcγR activation has not been undertaken (Bakalar et al, 2018). Our data suggest that antibody engineering strategies that optimize spacing of multiple antibodies through leucine zippers, cysteine bonds, DNA hybridization (Delcassian et al, 2013;Seifert et al, 2014;Sil, Lee, Luo, Holowka, & Baird, 2007) or multimeric scaffolds (Divine et al, 2020;Fallas et al, 2017;X. Huang et al, 2020;Ueda et al, 2020) could lead to stronger FcγR activation and potentially more effective therapies.…”

Hitchhiking on Controlled-Release Drug Delivery Systems: Opportunities and Challenges for Cancer Vaccines

“…By modulating the polymer molecular weight, composition, preparation method, particle size and additives, etc., MPs can provide sustained or pulsatile release of entrapped antigens over periods lasting weeks to months (Sivakumar et al, 2011). Furthermore, the modification of surface physicochemical properties or decoration with ligands or antibodies can lead to different functionalized MPs (Figure 2), such as APCs-targeting MPs, immune cell-engaging particles (artificial DCs) or MPs for intranasal vaccination (Mata et al, 2011;Li et al, 2016b;Jung et al, 2019;Koerner et al, 2019;Huang et al, 2020). Among the most extensively exploited synthetic polymers in many areas, PLGA has been approved by the FDA for human use in drug delivery and biomedical devices due to its biodegradability and biocompatibility (Koerner et al, 2019).…”

“…Besides, before encapsulated into the PLGA MPs, protein antigens can be previously loaded into polysaccharide (dextran) glassy particles through freezing-induced phase separation to protect antigen’s integrity ( Geng et al, 2008 ). In another example, antigens and other immunomodulators can be efficiently and intactly loaded on the surface of PLGA MPs by conjugating short synthetic DNA scaffolds to the surface ( Huang et al, 2020 ). More importantly, many advanced manufacturing processes, such as spray drying technology and supercritical carbon dioxide, are able to greatly improve the drug loading, protein stability, reproducibility and scaling-up production of PLGA MPs ( Han et al, 2016a ; Koerner et al, 2019 ).…”

Applications of scaffold-based advanced materials in biomedical sensing

“…Scaffolds can be generally categorized as ceramics [ 5 ], molecular [ [6] , [7] , [8] ], nanofiber [ 9 ], polymers [ 10 ], metal alloys [ 11 , 12 ], or composites [ 13 ] based on the type of compounds or materials that have been used in their construction. Scheme 1 illustrates some important scaffold-based materials.…”