Complete regression of metastatic de-differentiated liposarcoma with engineered mesenchymal stromal cells with dTRAIL...

De-differentiated liposarcoma (DDLPS) is a rare cancer with high rates of recurrence and metastasis. Currently, treatment with doxorubicin-ifosphamide, following surgical resection, is routinely performed. However, clinical treatment of these refractory cancers require further study. We investigated the treatment of mesenchymal stromal cells (MSC) transduced with dodecameric tumor necrosis factor receptor apoptosis-inducing ligand (dTRAIL) and herpes simplex virus thymidine kinase (HSV-TK) (MSC-TR/TK), as a method to approach DDLPS therapy. First, in order to assess the efficacy of this therapy, cell viability was evaluated by apoptosis analysis of a DDLPS cell line co-cultured with patient-derived cells (PDCs) and MSC-TR/TK in vitro. In vivo, we established a lung metastasis model using the DDLPS cell line and assessed the anti-tumorigenic efficiency of dTRAIL-TK by injecting MSC-TR/TK. Results confirmed that liposarcoma cells resistant to dTRAIL in PDCs, transformed by HSV-TK, induced apoptosis effectively after treatment with toxic ganciclovir (GCV). Meanwhile, we observed that treatment of GCV after injection of MSC-TR/TK effectively eliminated lung nodules in a lung metastasis model established from LPS246 cells resistant to dTRAIL. When mice were treated with GCV two days after double injection with MSC-TR/TK, the tumor suppression effect was even more pronounced.