Sk. Mendiratta et al., Therapeutic tumor immunity induced by polyimmunization with melanoma antigens gp100 and TRP-2, CANCER RES, 61(3), 2001, pp. 859-863
To improve the immunogenicity of melanoma self-antigens, we used a novel st
rategy of nonviral genetic vaccination coupled with muscle electroporation.
Electroporation-enhanced immunization with plasmids encoding either human
gp100 or mouse TRP-2 antigens induced only partial rejection of B16 melanom
a challenge. However, immunization with a combination of these two antigens
caused tumor rejection in 100% of the immunized mice. Splenocytes from com
bination-immunized animals killed syngeneic targets loaded with peptides de
rived from both gp100 and TRP-2. Immune fell depletion experiments identifi
ed CD8(+) T lymphocytes as the primary effecters of antitumor immunity. Mos
t importantly, polyimmunization led to the generation of a therapeutic immu
ne response that significantly improved the mean survival time of mice bear
ing established lung metastases. These results validated the usefulness of
electroporation-enhanced, nonviral genetic immunization for the active immu
notherapy of cancer and indicated that using a combination of different tum
or antigens may be a decisive strategy for a successful therapeutic vaccina
tion.