Table 1.

Applications of cellular vesicles in cancer immunotherapy.

Strategies	Intervention	Parental cell	Mechanisms	Tumor models	References
Genetic engineering	CAR-T cell vesicle-coated nanoparticle	T cell	GPC3-specific CAR-T membrane vesicles were used to wrap IR780-loaded mesoporous silica nanoparticles for tumor targeting and photothermal therapy.	Xenograft model of human liver cancer.	(38)
	SIRPα and PD-1	Tumor cell	Tumor cells were programmed to overexpress SIRPα and PD-1 and then extracted for cellular vesicles to simultaneously block innate and adaptive immune checkpoints in vivo.	Breast cancer and melanoma models. Recurrence and metastasis model of breast cancer.	(10)
Membrane hybridizaiton	Various cell membranes	Two types of tumor cells; Macrophage, platelet and tumor cell	Hybridization of two or more types of cellular vesicles from tumor cells, erythrocytes, platelets and immune cells to achieve the multiple functions of escaping clearance, targeting tumor leison and activating antitumor immunity.	Primary, recurrence and metastasis tumor model of breast cancer and melanoma.	(10, 14)
	Cell membrane and bacterial membrane	Tumor cell and bacterium	Tumor cell vesicles were fused with E. coli membrane vesicles to stimulate dendritic cell maturation and T cell activation for personalized cancer vaccines and immunotherapy.	Breast and colon cancer models. Lung metastasis model of breast cancer.	(56, 62)
	Cell membrane and drug-loaded liposome	Macrophage; Natural killer cell	Liposomes carrying antitumor drugs (emtansine or doxorubicin) were hybridized with macrophage or NK cell vesicles for targeted cancer therapy through interactions of α4β1/VCAM-1 and NKG2-D and its ligands, respectively.	Lung metastasis model of breast cancer. Xenograft tumor model of human cancer cells.	(9, 41)
Drug encapsulation	DC vesicles, oxaliplatin-loaded nanoparticles and αPD-L1	Dendritic cell	Oxaliplatin encapsulated in cellular vesicles resulted in immunogenic cell death, followed by DC vesicle presentation of tumor antigens to initiate T-cell responses. They also displayed synergistic antitumor effect when combined with anti-PD-L1 therapy.	Mouse model of colon cancer.	(43)
	Erythrocyte vesicles and oncolytic virus	Erythrocyte	Oncolytic viruses were encapsulated into bioengineered cell vesicles to evade antiviral neutralizing antibodies, reduce systemic toxicity and enhance targeting delivery.	Human liver cancer xenograft tumor model.	(70)
	T cell vesicle-coated nanoparticle	T cell	T cell vesicles retained LFA-1, PD-1, TGF-βR and FasL. They actively targeted tumor tissues through LFA-1/ICAM-1 interaction, rescued antitumor effects of CD8+ T cells by blocking PD-1 and TGF-β, and directly induced apoptosis of tumor cells via Fas/FasL axis.	Subcutaneous tumor models of melanoma and lung cancer. Lung metastasis model of melanoma.	(39)
	Neutrophil vesicle-coated drug-loaded nanoparticle	Neutrophil	Carfilzomib-loaded nanoparticles were encapsulated in neutrophil-derived vesicles. Neutrophil vesicles targeted circulating tumor cells and premetastatic lesion through three pairs of interactions including LFA-1/ICAM-1, β1 integrin/VCAM-1, and CD44/L-selectin.	Lung metastasis and premetastatic mouse model of breast cancer.	(42)
	Monocyte vesicle-coated drug-loaded nanoparticle	Monocyte	Doxorubicin-loaded PLGA nanoparticles were coated with monocyte-derived vesicles to achieve tumor targeting through the interaction of α4β1 integrin with VCAM-1.	Human breast cancer xenograft model.	(40)
Exogenous stimulation	Granzyme B, PD-1 and TGF-β receptor	T cell	Cellular vesicles derived from activated T cells contained abundant granzyme B, PD-1 and TGF-β receptors and could exert tumoricidal effect as well as prevent T cell exhaustion.	Mouse model of lung cancer.	(13)
	mRNAs of pro-inflammatory cytokines and αPD-L1	Macrophage	Vesicles extruded from M1 macrophages carried high levels of mRNA of pro-inflammatory cytokines such as IL-6 and TNF-α. They could promote the polarization of macrophages toward M1 type and enhance antitumor efficacy of anti-PD-L1 therapy.	Mouse model of colon cancer. Recurrence and metastasis model of breast cancer and melanoma.	(11, 14)