ThermoDox (lyso-thermosensitive liposomal doxorubicin)

In this study, we investigated whether mEHT accelerates the tumor-specific delivery of doxorubicin (DOX) from lyso-thermosensitive liposomal doxorubicin (LTLD) and improves its anticancer efficacy in mice bearing a triple-negative breast cancer cell line (4T1)...The body weight loss was similar in all mice treated with any DOX formulation, suggesting no difference in toxicity. In conclusion, LTLD combined with mEHT represents a novel approach for DOX delivery into cancer tissue.

Our group previously developed and characterized a thermosensitive liposome formulation of the heat shock protein 90 inhibitor alvespimycin as a companion therapeutic to a thermosensitive liposome formulation equivalent in composition to ThermoDox (i.e., ThermoDXR), with the goal of increasing the therapeutic index of doxorubicin as the combination was revealed to be highly synergistic in a panel of human breast cancer cell lines including MDA-MB-231 (Dunne et al., 2019). The data presented here further describes the effect of the doxorubicin (DXR) and alvespimycin (ALV) combination in vitro and in vivo. Specifically, the combination effect in mouse breast cancer 4T1 cells and the in vivo efficacy of this heat-activated chemotherapy combination in both immunocompromised (MDA-MB-231 tumor bearing female SCID mice) and immunocompetent (4T1 tumor bearing female BALB/c mice) models of breast cancer.

This early phase study builds on previous work targeting tumours in the liver to investigate whether enhancement of chemotherapy delivery using ultrasound-mediated hyperthermia can be translated to the stroma-dense environment of pancreatic ductal adenocarcinoma. If successful, it could herald a new approach towards managing these difficult-to-treat tumours.

This is to be achieved by combining Lyso-Thermosensitive Liposomal Doxorubicin (LTLD, ThermoDox, Celsion Corporation, Lawrenceville, NJ, USA) with mild local hyperthermia, induced by Magnetic Resonance guided High Intensity Focused Ultrasound (MR-HIFU). Results will be published in an academic peer-reviewed journal. NCT03749850, EudraCT 2015-005582-23.