Table 2 Engineered EVs for immunotherapy-related cancer combination therapy
From: Engineered extracellular vesicles: potentials in 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] |