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2004 OCT 6 - (NewsRx.com & NewsRx.net) -- The ubiquitin-fusion degradation pathway plays an indispensable role in naked DNA vaccination with a chimeric gene encoding a syngeneic cytotoxic T lymphocyte epitope of melanocyte and green fluorescent protein.
According to published research from Japan, "Antitumor immunity against murine melanoma B16 was achieved by genetic immunization with a naked chimeric DNA encoding a fusion protein linking green fluorescent protein (GFP) to the N-terminus of a major CD8+ cytotoxic T lymphocyte (CTL) epitope of tyrosinase-related protein 2 (TRP-2[subscript]181-188) of murine melanoma, designated as pGFP-TRP-2. Tumor growth was profoundly suppressed in C57BL/6 mice immunized with pGFP-TRP-2, while mice vaccinated with pTRP-2 showed rapid tumor growth and died within 40 days after tumor challenge. Splenocytes of mice immunized with pGFP-TRP-2 showed high CTL activity specific for TRP-2[subscript]181-188."
"GFP-TRP-2 expressed in COS-7 cells was rapidly degradated in vitro and the degradation was almost completely prevented by adding a proteasome inhibitor, MG-132, in the culture," said Manxin Zhang and collaborators at Kyushu University and the Tokyo Metropolitan Institute of Medical Science. "Furthermore, the antimelanoma immunity induced by genetic immunization with pGFP-TRP-2 was completely cancelled in mice deficient in proteasome activator PA28alpha/beta. Taken together, GFP-TRP-2 processed by cytosolic proteasome played a central role in breaking peripheral tolerance to a melanoma/melanocyte antigen, TRP-2[subscript]181-188, by activating CD8+ CTL specific for TRP-2[subscript]181-188."
"TRP-2[subscript]181-188 fused to GFP may be ...