Focused Ultrasound and Bubble Liposomes Combined Tumor Immunomodulation

Abstract

It is well-established that the stimulation of immune system of a patient by monoclonal antibodies, adoptive dendritic cell transfer and in situ vaccines can enhance antitumoral effects. Despite this, the progression-free survival achieved by these methodologies provides a modest improvement over traditional cancer treatment. To overcome these barriers, we hypothesize that focused ultrasound (FU) in combination with bubble liposomes (BL) will induce cellular stress, and elicit micro-environmental changes to induce a potent antitumor response. The objective of the proposed project is to test the feasibility of BL/FU approach against colon cancer in vitro and in vivo.

Mice bearing C26 colon cancer were treated with FU heating and BL. Flow cytometric analysis was conducted to understand the maturation of DCs and macrophages. CytoTox 96® Assay as used to determine T cell-mediated tumor cell lysis. Real-Time gene expression studies were conducted to identify inflammatory cytokines.

FU and BL induced dendritic cell maturation and CTL mediated lysis of tumor cells in vitro. Significantly enhanced infiltration of cytotoxic T-cells in colon tumor was observed 4-fold difference for FU/BL compared to control. Hyperthermia (~42ºC) and BL treatment of RAW 264.7 macrophages induced an M1 phenotype compared to control in-vitro.

Hyperthermia and liposomal nanoparticle treatment induce M1 polarization. FU and BL treatment sensitizes colon carcinoma CT26 cancer cells to the CTLs antitumor response. This technology has the potential for improving immunotherapy response in clinics.