Tumor Radiosensitization by Gene Electrotransfer-Mediated Double Targeting of Tumor Vasculature

Area of Science:

• Oncology
• Gene Therapy
• Cancer Immunology

Background:

• Targeting tumor vasculature via endothelial cell markers aids radiosensitization.
• Endoglin (CD105) and melanoma cell adhesion molecule (CD1046) are key targets on tumor vasculature.
• Previous in vitro studies developed a plasmid for simultaneous silencing of CD105 and CD1046.

Purpose of the Study:

• To evaluate the in vivo therapeutic potential of gene electrotransfer-mediated delivery of a novel plasmid targeting CD105 and CD1046.
• To investigate the combined effects of this gene therapy and tumor irradiation.
• To elucidate the underlying therapeutic mechanisms and immune response activation.

Main Methods:

• Gene electrotransfer of a plasmid targeting CD105 and CD1046 in a murine mammary adenocarcinoma (TS/A) model.
• Combination therapy with tumor irradiation.
• Assessment of antitumor effects (tumor growth delay, tumor-free survival).
• Histological analysis (vascularization, proliferation, hypoxia, necrosis, apoptosis, immune cell infiltration).
• Evaluation of immune response (STING, pro-inflammatory cytokines via qRT-PCR).

Main Results:

• Significant radiosensitization was observed with the combined gene therapy and irradiation approach.
• The therapy demonstrated a notable antitumor effect in the radioresistant and immunologically cold TS/A tumor model.
• Histological analysis revealed modulation of tumor microenvironment, and immune response markers (STING, cytokines) showed induction.

Conclusions:

• Gene electrotransfer of the dual-target silencing plasmid combined with irradiation is a promising radiosensitizing strategy.
• This approach shows therapeutic potential in challenging tumor models, suggesting broad applicability.
• The findings support this gene therapy as a novel treatment modality for diverse tumors.