Targeting cell surface glucose-regulated protein 94 in gastric cancer with an anti-GRP94 human monoclonal antibody
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Gastric cancer (GC), a leading cause of cancer-related mortality,remains a significant challenge despite recent therapeuticadvancements. In this study, we explore the potential of targetingcell surface glucose-regulated protein 94 (GRP94) withantibodies as a novel therapeutic approach for GC. Our comprehensiveanalysis of GRP94 expression across various cancertypes, with a specific focus on GC, revealed a substantial overexpressionof GRP94, highlighting its potential as a promisingtarget. Through in vitro and in vivo efficacy assessments, aswell as toxicological analyses, we found that K101.1, a fullyhuman monoclonal antibody designed to specifically target cellsurface GRP94, effectively inhibits GC growth and angiogenesiswithout causing in vivo toxicity. Furthermore, our findingsindicate that K101.1 promotes the internalization and concurrentdownregulation of cell surface GRP94 on GC cells. Inconclusion, our study suggests that cell surface GRP94 may bea potential therapeutic target in GC, and that antibody-basedtargeting of cell surface GRP94 may be an effective strategy forinhibiting GRP94-mediated GC growth and angiogenesis.
Abstract
Gastric cancer (GC), a leading cause of cancer-related mortality,remains a significant challenge despite recent therapeuticadvancements. In this study, we explore the potential of targetingcell surface glucose-regulated protein 94 (GRP94) withantibodies as a novel therapeutic approach for GC. Our comprehensiveanalysis of GRP94 expression across various cancertypes, with a specific focus on GC, revealed a substantial overexpressionof GRP94, highlighting its potential as a promisingtarget. Through in vitro and in vivo efficacy assessments, aswell as toxicological analyses, we found that K101.1, a fullyhuman monoclonal antibody designed to specifically target cellsurface GRP94, effectively inhibits GC growth and angiogenesiswithout causing in vivo toxicity. Furthermore, our findingsindicate that K101.1 promotes the internalization and concurrentdownregulation of cell surface GRP94 on GC cells. Inconclusion, our study suggests that cell surface GRP94 may bea potential therapeutic target in GC, and that antibody-basedtargeting of cell surface GRP94 may be an effective strategy forinhibiting GRP94-mediated GC growth and angiogenesis.
참고문헌 (27)
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