Combination Therapy of JO-1 and Chemotherapy in Ovarian Cancer Models.

摘要

A manufacturing protocol for JO-1 with and without His-tag at large scale has been established. - There were no adverse effects after intravenous injection of JO-1 in DSG2 transgenic mice. - JO-1 has favorable pharmacokinetics parameters. - The effect of JO-1 on normal tissues is minimal because DSG2 is trapped in epithelial junctions in normal tissues and not accessible to intravenously injected JO-1. - JO-1 enhances Doxil chemotherapy in xenograft models of ovarian cancer and in mouse models with syngeneic tumors. - JO-1 continues to be effective after multiple treatment cycles even in the presence of detectable antibodies. - JO-1 facilitates pre-existing anti-tumor T-cell responses. - An affinity-enhanced version of JO-1 (called JO-4) was produced. - JO-4 co-therapy allows for reduction of effective Doxil dose in a xenograft model of ovarian cancer. - JO-4 increases the therapeutic effect of Doxil on lymphogenic metastases. - Combined treatment with JO-4 and Doxil is safe in non-human primates