Table 4 Engineered EVs as immune checkpoint blocking agent for cancer immunotherapy

T-cell-derived EV mimetics

Not specified

Enhance tumor targeting, improve photothermal therapy efficacy

PD1-enriched T-cell membrane EV mimetics increase tumor accumulation and immune recognition

[159]

Genetically engineered PD1-enriched EVs

Not specified

Immune checkpoint blockade, promote immune recognition

Engineered PD1-enriched EVs to reduce immune suppression by tumor-derived exosomes (TEXs)

[93]

Bacterial outer membrane vesicles (OMVs)

Not specified

Enhance immune activation, PD1 blockade

Engineered OMVs expressing PD1 external domain, maintaining immune-stimulating properties

[103]

Bacterial outer membrane vesicles (OMVs)

Mouse colon cancer

Enhance tumor targeting and immune response

LyP1-modified OMVs deliver PD1-encoding plasmids to tumor cells, recruit CTLs, and induce IFN-γ

[160]

Tumor-repopulating cell-derived microparticles (DOX^@3D-MPs)

Various tumor types

Enhance ICB therapy efficacy, induce immunogenic cell death

Delivering doxorubicin (DOX) to promote antigen presentation and CD8⁺ T cell activation, enhancing immune memory

[161]

Tumor-derived exosomes (T-EXOs)

Not specified

Improve ICB therapy outcomes, enhance CD8⁺ T cell function

Disrupting T-EXOs with antiviral peptide, improving immune microenvironment, preventing premetastatic niche formation

[162]

Tumor-derived EVs (TuEVs)

Not specified

Reduce ICI-related cardiotoxicity, enhance ICI therapy safety and efficacy

Bioorthogonal metabolic engineering to couple myocardial-targeting peptides with PD-L1 on TuEVs, inhibiting T-cell activity

[163]

Ultrasound contrast agent EVs (Gp-EVtPD1)

Not specified

Enhance anti-tumor immune response, improve therapeutic efficacy

EVs displaying truncated PD1 and encapsulated in Ca(HCO3)2, used for imaging and PD-L1 degradation, promoting anti-tumor immunity

[164]

Plasma EVs (EV pPD-L1)

Non-small-cell lung cancer (NSCLC)

Rapid assessment of PD-L1 phosphorylation status, assist patient selection

Measuring phosphorylation status of PD-L1 in plasma EVs (EV pPD-L1) for clinical selection

[165]

Bispecific EVs (BsEVs)

Not specified

Target tumor antigens and immune checkpoint proteins simultaneously, enhance tumor targeting

Engineered bispecific EVs to target tumor antigens and block immune checkpoints, reversing immunosuppressive landscape

[166]

Probiotic-derived EVs

Colorectal cancer

Improve anti-PD-1 immunotherapy efficacy, modulate gut immunity

EVs from Lactobacillus rhamnosus GG improving gut immunity, enhancing anti-PD-1 therapy efficacy

[167]

Milk-derived EVs

EGFR⁺ tumors

Restore CD8⁺ T cell activity, inhibit tumor growth

Targeting M2 tumor-associated macrophages, delivering siPDL1 to repolarize to M1 phenotype, restoring immune response and inhibiting tumor growth

[168]