Thermal ablation enhances immunotherapeutic effect of IP-001 on orthotopic liver cancer in a rat model.

Abstract

Background: Thermal ablation is reported to increase immunogenicity in tumor cells via expressing tumor antigens. IP-001, a synthesized molecule, is created by attaching galactose molecules to the free amino groups of partially deacetylated glucosamine polymers. As a member of a new class of polycationic immunoadjuvants that activate multiple immune response pathways, IP-001 can both sequester ablation-released tumor antigens in situ and independently recruit and stimulate antigen presenting cells (APCs) to induce a potent tumor-specific Th1 type T cell response.

Methods: An orthotopic HCC rat model is established by implantation of 5 × 10⁶ N1-S1 cells into the left lobe of liver. When tumor size reached 1.0-1.5 cm³, the animals were divided randomly into 4 groups, (1) MWA+IP-001; (2) MWA+saline; (3) sham MWA+IP-001 and (4) sham MWA+saline (n = 5 each group).

Results: IP001 + MWA treatment significantly suppressed tumor growth in comparison to the other 3 groups. Significantly increased infiltration of inflammatory/immune cells were found in the tumor adjacent tissues of MWA+IP-001 mice, compared to the other 3 groups. Flow cytometry results indicated that there were significant increases of cytotoxic T cells, macrophages, dendritic cells and NK cell in the combination of MWA and IP001 treated mice, compared to other 3 groups (p < 0.01). Significantly decreased number of Treg cells were found in all the treatment arms compared to untreated control (p < 0.01).

Conclusion: Combination of MWA and IP001 enhances tumor suppression in an orthotopic HCC rat model. The tumor suppression is associated to the enhanced immune responses in terms of recruiting the important cell subpopulations such as CD8 + T-cells and NK cells into tumor microenvironment and abolishing immune suppressor such as Treg cells.