Antibody targeting GRP78 enhances the efficacy of radiation therapy in human glioblastoma and non-small-cell lung cancer cell lines and tumor models
Menée sur des lignées cellulaires de glioblastome multiforme et de cancer du poumon non à petites cellules puis à l'aide de xénogreffes sur des modèles murins, cette étude montre qu'un anticorps ciblant la protéine GRP78 peut augmenter l'efficacité d'une radiothérapie
Purpose : Non-small-cell lung cancer (NSCLC) and glioblastoma multiforme (GBM) have poor median survival. NSCLC and GBM overexpress glucose regulated protein 78 (GRP78), which has a role in radioresistance and recurrence. In this study, we determined the effect of anti-GRP78 antibody and the combined effect of the anti-GRP78 antibody with ionizing radiation (XRT) on NSCLC and GBM cell lines both in vitro and in vivo. Experimental Design : NSCLC and GBM cancer cell lines were treated with anti-GRP78 antibodies and evaluated for proliferation, colony formation, cell death and PI3K/Akt/mTOR signaling. The efficacy of anti-GRP78 antibodies on tumor growth in combination with radiation (XRT) was determined in vivo in mouse xenograft models. Results :GBM and NSCLC cells treated with anti-GRP78 antibodies showed attenuated cell proliferation, colony formation, and enhanced apoptosis. GBM and NSCLC cells treated with anti-GRP78 antibodies also showed global suppression of the PI3K/Akt/mTOR signaling. Combining antibody with XRT resulted in significant tumor growth delay in both NSCLC and GBM heterotopic tumor models. Conclusions :Antibodies targeting GRP78 exhibited antitumor activity and enhanced the efficacy of radiation in NSCLC and GBM both in vitro and in vivo. GRP78 is a promising novel target, and anti-GRP78 antibodies could be used as an effective cancer therapy alone or in combination with XRT.