Targeting folate receptor β positive tumor-associated macrophages in lung cancer with a folate-modified liposomal...

Area of Science:

• Oncology
• Immunology
• Nanomedicine

Background:

• Tumor-associated macrophages (TAMs) promote cancer progression, invasion, angiogenesis, metastasis, inflammation, and immunosuppression.
• Folate receptor β (FRβ) is overexpressed on TAMs, but its clinical significance in lung cancer is unclear.
• FRβ overexpression in lung cancer TAMs correlates with poor prognosis.

Purpose of the Study:

• To investigate the clinical significance of FRβ-positive macrophages in lung cancer.
• To develop a novel targeted gene therapy for lung cancer using folate-modified lipoplexes (F-PLP) to target FRβ-positive TAMs and cancer cells.
• To evaluate the efficacy and safety of F-PLP delivering a BIM-S plasmid (F-PLP/pBIM) in preclinical lung cancer models.

Main Methods:

• Verified FRβ overexpression in lung cancer TAMs and its association with prognosis.
• Utilized folate-modified lipoplexes (F-PLP) to deliver a BIM-S plasmid (pBIM).
• Administered F-PLP/pBIM to lung cancer cell lines (LL/2, MH-S) and mouse models (LL/2, A549) for in vitro and in vivo studies, including safety evaluation.

Main Results:

• F-PLP/pBIM induced apoptosis in lung cancer cells and FRβ-positive macrophages.
• In vivo administration of F-PLP/pBIM significantly depleted FRβ-positive macrophages and reduced tumor growth in lung cancer models.
• F-PLP/pBIM treatment inhibited tumor proliferation, angiogenesis, and overall tumor growth, demonstrating therapeutic efficacy.

Conclusions:

• FRβ-positive macrophages are significant in lung cancer prognosis.
• Folate-modified lipoplexes represent a novel targeted therapy for lung cancer by modulating the tumor microenvironment.
• F-PLP/pBIM shows potential as an effective and safe gene therapy for lung cancer, targeting both cancer cells and TAMs.