A metastatic
brain tumor is the most common type of
malignancy in the central nervous system, which is one of the leading causes of death in patients with
lung cancer. The purpose of this study is to evaluate the efficacy of a novel treatment for metastatic
brain tumors with
lung cancer using neural stem cells (NSCs), which encode rabbit
carboxylesterase (rCE) and the secretion form of
tumor necrosis factor-related apoptosis-inducing
ligand (sTRAIL). rCE and/or sTRAIL were transduced in immortalized human fetal NSCs, HB1.F3. The cytotoxic effects of the therapeutic cells on human
lung cancer cells were evaluated in vitro with the
ligands and decoy receptor expression for sTRAIL in the presence of
CPT-11. Human NSCs encoding rCE (F3.CE and F3.CE.sTRAIL) significantly inhibited the growth of
lung cancer cells in the presence of
CPT-11 in vitro.
Lung cancer cells were inoculated in immune-deficient mice, and therapeutic cells were transplanted systematically through intracardiac arterial injection and then treated with
CPT-11. In resting state, DR4 expression in
lung cancer cells and DcR1 in NSCs increased to 70% and 90% after
CPT-11 addition, respectively. The volumes of the
tumors in immune-deficient mice were reduced significantly in mice with F3.CE.sTRAIL
transplantation and
CPT-11 treatment. The survival was also significantly prolonged with treatment with F3.sTRAIL and F3.CE plus
CPT-11 as well as F3.CE.sTRAIL plus
CPT-11. NSCs transduced with rCE and sTRAIL genes showed a significant anti-
cancer effect on brain metastatic
lung cancer in vivo and in vitro, and the effect may be synergistic when rCE/
CPT-11 and sTRAIL are combined. This stem-cell-based study using two therapeutic genes of different
biological effects can be translatable to clinical application.