Advancing engineered nanoparticles for enhanced efficacy in cancer immunotherapy: optimizing nanoparticles for cancer immunotherapy.

Recent evidence on resistance to immune checkpoint inhibitors (ICIs) has necessitated the exploration of alternative cancer therapies with increased treatment responsiveness among patients, especially for solid tumors. Phototherapy with red or near-infrared light is considered as one such potential approach, but it espouses limited efficacy in treating solid tumors and aggravates cancer progression in some instances. In contrast, genetically engineered T cells bearing chimeric antigen receptors (CAR) targeting tumor-specific neo-antigens have demonstrated significant therapeutic potential and have advanced into clinical trials. Several reports have annotated numerous neo-antigens, eventually enhancing CAR T-cell design and efficacy. Nevertheless, numerous clinical trials envisaged 'hyperimmune response' as a limitation of effective CAR T treatment for cold tumors, driving the development of CAR engineered macrophages (CAR M) and natural killer (CAR NK) cells which efficiently infiltrated cold tumors and elicited better treatment response. CAR NK therapy is advantageous for its MHC independent cytotoxicity which prevents cytokine storm along with graft versus host disease (GVHD). However, isolation, gene manipulation and proliferation of the immune cells from patients is not time efficient. Involving nanotechnology has enhanced the time and CAR DNA delivery dependent efficacy of CAR therapy in all immune cells. Nanoparticles containing cationic polymers like polyethyleneimine (PEI), poly(L-lysine), and poly(2-dimethylamino) ethyl methacrylate effectively delivers DNA to the specific immune cells, thereby increasing the responsiveness towards the CAR therapy. In this review, we highlight promising avenues with potentials to improve clinical outcomes that have emerged from the convergence of nanotechnology and CAR based immunotherapy.