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- W3204014321 abstract "Zolbetuximab, a chimeric IgG1 monoclonal antibody, binds to Claudin 18.2 and mediates cancer death via antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. Phase III studies of zolbetuximab plus chemotherapy (fluoropyrimidine and oxaliplatin) are ongoing. Along with chemotherapy, immunotherapy is becoming standard of care for gastric cancer. The beneficial effect of zolbetuximab plus chemotherapy or anti-mouse PD-1 (anti-mPD-1) antibody is presented here. In this study, we examined the effect of zolbetuximab plus 5-fluorouracil + oxaliplatin (chemotherapy; Study 1) or an anti-mPD-1 antibody (Study 2) in a syngeneic mouse tumor model with mouse Claudin 18.2-expressing CLS-103 gastric carcinoma cells. Tumor cells were inoculated into immune-competent NMRI mice. Rituximab, PBS + 5% glucose, and anti-trinitrophenol antibody were used as isotype controls or vehicle (Table). Tumor volumes were assessed in both studies. In Study 1, flow cytometry was used to analyze the frequency of immune cells in tumor tissues. In Study 1, tumor growth was inhibited by 65%, 42%, or 93%, in the zolbetuximab, chemotherapy, or combination groups, respectively. Tumor volume was significantly lower with the combination versus zolbetuximab (P < 0.05) or chemotherapy alone (P < 0.01). The frequency of tumor-infiltrating CD8+ T-cells was significantly higher with the combination versus control (P < 0.05). In Study 2, tumor growth was inhibited by 50%, 60%, or 91%, in the zolbetuximab, the anti-mPD-1 antibody, or combination groups, respectively. Tumor volume was significantly lower with the combination versus zolbetuximab (P < 0.01) or anti-mPD-1 antibody (P < 0.05). Zolbetuximab combined with chemotherapy or an anti-mPD-1 antibody more potently inhibited tumor growth, compared with each treatment alone, in a syngeneic tumor model.Table: 986PStudy groupsStudy 1, n=15 each groupStudy 2, n=12 each groupGroup 1: control (rituximab + PBS + 5% glucose)Group 1: control (rituximab + anti-trinitrophenol antibody)Group 2: zolbetuximab (zolbetuximab + PBS + 5% glucose)Group 2: zolbetuximab (zolbetuximab + anti-trinitrophenol antibody)Group 3: chemotherapy (rituximab + 5-FU + oxaliplatin)Group 3: anti-mPD-1 antibody (rituximab + anti-mPD-1 antibody)Group 4: combination (zolbetuximab + 5-FU + oxaliplatin)Group 4: combination (zolbetuximab + anti-mPD-1 antibody)Abbreviations: 5-FU, 5-fluorouracil; anti-mPD-1, anti-mouse PD-1. Open table in a new tab" @default.
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- W3204014321 date "2021-09-01" @default.
- W3204014321 modified "2023-10-15" @default.
- W3204014321 title "986P Antitumor effect of zolbetuximab combined with chemotherapeutic agents or an anti-mPD-1 antibody in syngeneic immune-competent mice" @default.
- W3204014321 doi "https://doi.org/10.1016/j.annonc.2021.08.1370" @default.
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