Mitoxantrone Combined with Engineered TRAIL-Nanovesicles for Enhanced Cancer Immunotherapy Via Converting Apoptosis...

Area of Science:

• Biomedical Engineering
• Cancer Research
• Immunotherapy

Background:

• Pyroptosis, an inflammatory cell death, is a promising cancer immunotherapy target.
• GSDME under-expression in tumors limits pyroptosis induction.
• Caspase-3 and GSDME are essential for pyroptosis execution.

Purpose of the Study:

• To develop a strategy for inducing pyroptosis in tumors.
• To overcome GSDME under-expression in cold tumors.
• To evaluate the therapeutic potential of engineered nanovesicles and chemotherapy combination.

Main Methods:

• Engineered cellular nanovesicles (NVs) presenting TRAIL (NV_TRAIL) were developed.
• NV_TRAIL were combined with mitoxantrone (MTO) to create MTO@NV_TRAIL.
• The combination therapy's efficacy was assessed in primary tumors and its immunotherapeutic potential evaluated.

Main Results:

• MTO@NV_TRAIL successfully inhibited tumor growth and metastasis by converting apoptosis to pyroptosis.
• Microparticles from pyroptotic cells showed cytotoxicity against other tumor cells.
• The treatment increased mature dendritic cells and activated T cells in the tumor microenvironment and draining lymph nodes.

Conclusions:

• Engineered nanovesicles combined with chemotherapy offer an alternative approach to induce cancer pyroptosis.
• This strategy shows potential for clinical antitumor therapy and cancer immunotherapy.
• The combination treatment demonstrated efficacy in inhibiting tumor progression and activating anti-tumor immunity.