Table 2 Application of NK-Exos used in CI with targeted Abs (markers) and features

CD56, Rab5B, CD63, NKG2D, NKp30, NKp46, NKp44, FasL and PFN

Jurkat (T cell leukemia), K562 (erythroleukemia), DAUDI (Burkitt lymphoma), SKBR3 (Metastatic breast adenocarcinoma), and 501mel (Metastatic melanoma)

NK-Exos reveals significant controlling immune responses and defense against tumors and infected cells

[154]

CD81, CD63, TSG101, NKp44, CD69, PD-1, Gzm A and B, NKp46, IFN-γ, LFA-1, CD16, NKG2D, DNAM1, PFN, NKp30

NALM-18 (Childhood B-ALL) and K562 (Erythroleukemia)

Effective combination immunotherapy of NK-Exos

with an efficient cytotoxic effect on tumor cells

[111]

Actin, Myosin, ERM proteins, Cytosolic GAPDH, HSP60, HSP70, MHC-I, MHC-II, CD9, CD63, CD81, CD82, Tsg101, and CD56

Human healthy donor NK cells and PBMCs

NK-Exos plays a promising role in supporting NK-mediated immunosurveillance and

increasing NK-mediated immune responses against tumor cells

[135]

CD63, GM130, Alix, Cytochrome-c, PFN, FasL, and β-actin

NK92-MI, human glioblastoma (D54), breast carcinoma (MDA-MB-231), anaplastic thyroid cancer (CAL-62), hepatic carcinoma (HepG2) cell lines, and xenograft mouse tumor model

Exos mimetics (NK-EM) have tumoricidal effects and targetability against tumor cells

[160]

CD63, ALIX, GM-13, β-actin, FasL, and PFN

B16F10 (Melanoma) cells,

Kidney Phoenix ™ -Ampho cells, and NK-92MI

NK-Exos exert high cytotoxic effects on melanoma cells

[113]

CD56, TSG101, ALIX, NKp30, NKp44, NKp46, KIR2DL1 and NKG2D

SK-N-SH and CHLA-255 (Neuroblastoma)

NK-Exos cells demonstrate higher toxicity and lethality against tumor cells than naive NK-Exos

[137]

CD63, Alix, GM130, GzmB, Calnexin, PFN, and FasL

In vivo: (BALB/c)

In vitro: U87/MG(/F) glioblastoma, and NK92-MI

Evidence of NK-Exos antitumor effects in both in vivo and in vitro models on glioblastoma cells

[112]

ALIX, TSG101, CD63, CD47, CXCR4, and Cytochrome C

CHLA-255 (Neuroblastoma), MDA-MB-231 (Breast cancer), and embryonic kidney cell lines 293 T

NN/NK-Exos cocktail has efficient cancer targeting and MiR tumor cells’ delivery

[145]

TSG101, Alix and CD63

Human NK-92 cells and MCF-7 (Breast cancer)

PTX-NK-Exos increased the apoptosis of tumor cells by increasing the expression of Caspase-3 and Bax

[21]

CD56 and CD63

NK-92MI cell line and lung cancer clinical samples

NK-Exos on-chip biogenesis show high cytotoxic effects

[110]

HIF-1α, FasL, PFN, and GzmB (functional markers)

MCF-7 (Human breast cancer), A2780 (Human ovarian adenocarcinoma), NK92-hIL-15, and NK92 (NK cells)

Hypoxia enhanced NK-Exos decrease tumor cells proliferation

[14]

BCL-2, CD63, and CD56

NK92M (NK cells), HEK293T (human embryonic kidney), K562 (Bone marrow), MEC-1 ( B-chronic lymphocytic leukemia), MCF-7, SKBR3, MCF-10A, T-47D, and MDA-MB-231 (breast cancer)

NK-Exos loaded anti-Bcl-2 siRNA induces apoptosis in breast cancer cells

[156]

GD2, CD56, CD16, CD3, and CXCR4

CHLA-136, LAN-5, and CHLA-255 (Neuroblastoma)

NK-Exosomal MiR-186 (suppressor) indicates cytotoxicity effect on neuroblastoma cells

[139]

CD63 and TSG10

Mia PaCa-2, and PANC-1(Primary pancreatic cancer)

NK cell Exosomal MiR (3607-3p) inhibits pancreatic cancer by targeting the IL-26

[147]