Grapefruit-Derived Vesicles Loaded with Recombinant HSP70 Activate Antitumor Immunity in Colon Cancer In Vitro and In...

Area of Science:

• Immunology
• Biotechnology
• Oncology

Background:

• Exogenous heat shock protein 70 (HSP70) shows promise as an adjuvant for antitumor immune responses.
• Plant extracellular vesicles, specifically grapefruit-derived extracellular vesicles (GEVs), can encapsulate proteins while preserving function.
• GEVs offer potential for enhanced antigen-presenting activity, bioavailability, and stability of exogenous HSP70.

Purpose of the Study:

• To evaluate the efficacy of HSP70 loaded into GEVs (GEV-HSP70) in eliciting an antitumor immune response.
• To assess the potential of GEV-HSP70 as a novel therapeutic strategy for colorectal cancer.

Main Methods:

• In vitro studies using human (HCT-116, DLD1) and mouse (CT-26) colorectal cancer cell lines.
• Assessment of cancer cell sensitivity to cytotoxic lymphocytes and NK-92 cells.
• In vivo studies using a colon carcinoma mouse model (BALB/c mice with CT-26 cells).

Main Results:

• GEV-HSP70 significantly increased cancer cell sensitivity to immune cells compared to free HSP70.
• The effective dose of GEV-HSP70 was 20 times lower than free HSP70 for immune activation.
• In vivo, GEV-HSP70 treatment reduced tumor size, decreased immunosuppressive factors (TGF-β1, IL-10), and increased CD8+ T cell accumulation, leading to improved animal survival.

Conclusions:

• HSP70 encapsulated in plant extracellular vesicles (GEV-HSP70) is a feasible and effective method for activating specific immune responses against colon tumors.
• This novel approach holds significant potential for developing new immunotherapies for colorectal cancer.