Systemic delivery of stem cells expressing an apoptosis-inducing protein can successfully incorporate into malignant pleural mesothelioma (MPM) cells and subsequently induce their death, according to preclinical study findings.
While further validation is needed, the research opens up the possibility of using stem cell therapy to decrease tumour burden in this rare and largely untreatable type of lung cancer.
“Bone marrow-derived mesenchymal stem cells (MSCs) are attractive candidates as vectors for anticancer therapies for a variety of reasons,” say Sam Janes (University College London, UK) and colleagues who performed the study.
Indeed, in vitro studies have shown that MSCs migrate towards tumour cells and in vivo studies that they can then incorporate into a variety of cancer cell types. This is true in a variety of cancer cell types, including lung metastases. MSCs can also be delivered intravenously as well as intrapleurally.
“In this study, we show for the first time that MSCs expressing TRAIL (MSCTRAIL) induce apoptosis in MPM cells in vitro,” Janes and team report in Thorax. TRAIL, or tumour necrosis factor-related apoptosis-inducing ligand, is a transmembrane protein and an “exciting anticancer molecule”, the team explains.
Recombinant TRAIL has been tested in early clinical trials and shown promising results, but its short half-life of 32 minutes means that it would require multiple infusions to have any sustained therapeutic effect.
“MSCs home to and incorporate into tumours in vivo when delivered via both intrapleural and intravenous routes,” the team notes, so using these cells to deliver TRAIL is an interesting prospect for malignant mesothelioma, which is often too diffuse to surgically remove or does not respond well to chemotherapy.
The researchers used a variety of methods to show that MSCTRAIL could kill MPM cells in vitro and then home in on, and kill, tumour cells in animal model of malignant mesothelioma. Dual fluorescence and bioluminescent imaging were used to track the movement of the stem cells.
While both intrapleural and intravenous delivery of the stem cells was able to decrease the tumour burden in mice, intravenous administration appeared to have a greater effect. MSCTRAIL also resulted in a greater level of cell death when compared with treatment with recombinant TRAIL in vitro.
“The therapeutic effect seen with intravenous delivery could be related to greater engraftment of MSCs within the tumour and is an important finding when considering the future therapeutic role of MSCTRAIL therapy in the clinic,” the researchers conclude.
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