A cascade targeting strategy based on modified bacterial vesicles for enhancing cancer immunotherapy

Area of Science:

• Biomedical Engineering
• Immunotherapy
• Nanotechnology

Background:

• PD-1 antibody immunotherapy is effective but limited by low response rates and excessive immune reactions.
• Improving the tumor immune microenvironment is crucial for enhancing anti-cancer therapies.

Purpose of the Study:

• To develop a novel therapeutic strategy to enhance PD-1 antibody efficacy.
• To reduce excessive immune responses associated with immunotherapy.

Main Methods:

• A biomimetic cascade targeting nanosystem, siRNA@PLOV, was developed by fusing photothermal sensitive liposomes (PTSLs) with attenuated Salmonella outer membrane vesicles (OMVs).
• The nanosystem was used in tumor therapy to target tumor tissues and T cells, incorporating CD38 silencing.
• siRNA@PLOV was administered, followed by anti-PD-1 antibody treatment.

Main Results:

• The fused PLOVs retained OMV biological characteristics and improved drug loading.
• OMV immunogenicity and photothermal effects increased T cell infiltration.
• CD38 silencing enhanced T cell cytotoxicity, particularly when combined with PD-1 antibody therapy.

Conclusions:

• Optimal anti-tumor efficacy was achieved when anti-PD-1 administration followed siRNA@PLOV treatment on day 5.
• This therapeutic regime induces "vaccine effects," showing potential for preventing tumor recurrence and improving patient prognosis.