PLGA-PEG-Mal used in development of Polymer-DNA based nanoparticles for immunotherapy of cancer

 

Maleimide is a chemical moiety that can chemically react with thiol (-SH) units at neutral pH and room temperature (i.e. gentle conditions unlikely to damage biomolecules) to bind to them. A useful property of this is attaching a biological molecule (protein, DNA, etc.) which has a thiol unit on it to synthetic polymer such as PEG-PLGA to create a combination semi-synthetic material. Recently, PLGA-PEG-Mal (AI053) from PolySciTech (www.polyscitech.com) used in development of polymer-DNA nanoparticles for use in immunotherapy approaches. This research holds promise to improve therapies against cancer. Read more: Huang, Xiao, Jasper Z. Williams, Ryan Chang, Zhongbo Li, Cassandra E. Burnett, Rogelio Hernandez-Lopez, Initha Setiady et al. "DNA scaffolds enable efficient and tunable functionalization of biomaterials for immune cell modulation." Nature Nanotechnology 16, no. 2 (2021): 214-223. https://www.nature.com/articles/s41565-020-00813-z

“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.”