Natural killer (NK) cells play an important role in combating infectious and malignant diseases and
interleukin-2 (IL-2) has been shown to promote proliferation and activation of NK cells in vitro and in vivo. Here we investigate the effects of local cationic
lipid-mediated
IL-2 gene transfer on intratumoral accumulation and activation of NK cells in a SCID mouse
tumor model. UM449 human
melanoma tumors in SCID mice received intratumoral
injections of
DMRIE/DOPE admixed with VR1103,
a DNA plasmid encoding the gene for human
IL-2. Dissagregated
tumor cells were tested for
IL-2 secretion and were characterized using
antibodies to asGM1, MAC-1, and F4/80
antigens.
Granzyme A, a proteolytic
serine esterase, was also measured in
tumor cell lysates.
IL-2 secretion from
tumors injected with VR1103:
DMRIE/DOPE peaked at 48 h after injection and fell to baseline levels on day 8. Intratumoral
granzyme A activity was significantly increased in
tumors injected with
IL-2 plasmid:
DMRIE/DOPE complexes, but not by an irrelevant plasmid
DNA:
DMRIE/DOPE control. Importantly, the growth of UM449
tumors was slowed in VR1103:
DMRIE/DOPE-injected
tumors. These results indicate that local cationic
lipid-mediated gene transfer of
IL-2 induces activation of intratumoral NK cells and slows
tumor growth.