Table 2.

Engineered EVs for immunotherapy-related cancer combination therapy

Scheme	Principle/mechanism	Source of EV	EV type	Engineering strategy	Cargoes	Membrane modification	Effects	Refs.
Immunotherapy combined with chemotherapy	Co-delivery of chemotherapeutic drugs and immunomodulator. Chemotherapy induce ICD and activate immune effector cells	Fibroblasts	Thermosensitive exosome—liposome hybrid nanoparticle	Fusion of engineered exosomes and drug-loaded thermosensitive liposomes by freeze—thaw method	GM-CSF and docetaxel	CD47 overexpression	Inhibited tumor development	[45]
		BM-MSCs	Exosomes	Electroporation was applied to load galectin-9 siRNA, OXA-MAL was added to the exosomes via vortexing	Galectin-9 siRNA	OXA	Elicited anti-tumor immunity and inhibited tumor growth	[96]
Immunotherapy combined with PDT or PTT	Co-delivery of immunostimulatory and PS or PTA. PDT and PTT can induce ICD and covert “cold” tumor into “hot” tumor	MSCs	EVs	Turbulence induced high-yield production of MSC-derived EVs encapsulating mTHPC	Photosensitizer mTHPC		Permitted important tumoral necrosis and decreased intratumor proliferation	[99]
		CT26 cells	Hybrid vesicles	Fusion of exosomes and thermosensitive liposomes	ICG and adjuvant R837	CD47 overexpression	Eliminated the tumors	[100]
ICI combined with anti-ICI resistance treatment	Anti-ICI resistance treatment could improve ICI resistance	RAW264.7 macrophages	Microparticles	RAW264.7 macrophages were incubated with DSPE-PEG-Man and then were treated with metformin	Metformin	Mannose	Improved anticancer efficacy and long-term memory immunity	[104]
Therapeutic cancer vaccine combined with immune checkpoint blockade	Engineered EVs as vaccines, ICI can boost and maintain the vaccine’s effect to produce persistent responses	B16F10 cells/CT26 cells	Tumor-derived microparticles (T-MPs)	Incubated nano-Fe3O4 with producing cells, the obtained MPs were incubated with CpG-loaded liposome	Nano-Fe3O4	CpG-loaded liposome	Inhibited tumor progression	[34]
		BMDCs	Exosomes	Exosomes prepared from ovalbumin-pulsed, activated DCs were modified with anti-CTLA-4 antibody		Anti-CTLA-4 antibody	Slowed down tumor growth	[114]

GM-CSF granulocyte–macrophage colony-stimulating factor; OXA oxaliplatin; MAL N-(2-Aminoethyl) maleimide; PDT photodynamic therapy; PTT photothermal therapy; PS photosensitizers; PTA photothermal agents; ICD immunogenic cell death; ICG indocyanine green; mTHPC meta(tetrahydroxyphenyl)-chlorin; ICI immune checkpoint inhibitors