The number of tumor-infiltrating lymphocytes is known to be related to outcomes in patients with a variety of
malignancies.
Interferon (IFN) gamma-inducible protein-10 (IP-10) and monokine induced by IFNgamma (MIG) have chemotactic effects on activated T lymphocytes and natural killer (NK) cells. The aim of this study was to evaluate the antitumor effects of exogenous expression of the MIG and IP-10 genes delivered to solid
tumors by poly [D,L-2,4-diaminobutyric
acid] (
PDBA). The murine MIG and IP-10 genes were transfected into mouse
neuroblastoma cells with
PDBA. MIG and IP-10 levels in supernatants of transfected cells were measured by
enzyme-linked
immunosorbent assay. The chemotactic activities of MIG and IP-10 in the supernatants of cell cultures were measured by chemotaxis assay.
Tumors were injected in vivo with
PDBA/pmMIGColon, two colonsIP-10 complexes to evaluate the effects of these genes on
tumor volume and survival time of mice. Transfected
PDBA/pmMIGColon, two colonsIP-10 complexes produced MIG and IP-10
protein in vitro. MIG and IP-10
proteins secreted into the culture medium showed chemotactic activity. MIG and IP-10 gene therapy with the
PDBA system in vivo significantly inhibited
tumor growth and prolonged survival time of mice. In conclusion,
PDBA-mediated MIG and IP-10 gene therapy may be useful for treatment of solid
tumors.