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Supplementary Figure 2 from Pegfilgrastim Enhances the Antitumor Effect of Therapeutic Monoclonal Antibodies

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posted on 2023-04-03, 14:49 authored by Sébastien Cornet, Doriane Mathé, Kamel Chettab, Anne Evesque, Eva-Laure Matera, Olivier Trédan, Charles Dumontet

The tumor growth inhibition (TGI) was calculated on day 59 and 69 for untreated group and treated groups, respectively. The control group was sacrificed at day 59 as the tumor reached the maximum tolerated tumor size (2000 mm3) and the treated groups were maintained until day 69. In this preliminary experiment we demonstrated a potentiation of rituximab antitumor activity and extended mice survival when co-injected with pegfilgrastim. The results are reported and displayed as the mean {plus minus} SEM of six mice per group

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ARTICLE ABSTRACT

Therapeutic mAbs exert antitumor activity through various mechanisms, including apoptotic signalization, complement-dependent cytotoxicity, and antibody-dependent cellular cytotoxicity (ADCC) or phagocytosis (ADCP). G-CSF and GM-CSF have been reported to increase the activity of antibodies in preclinical models and in clinical trials. To determine the potential role of pegfilgrastim as an enhancer of anticancer antibodies, we performed a comparative study of filgrastim and pegfilgrastim. We found that pegfilgrastim was significantly more potent than filgrastim in murine xenograft models treated with mAbs. This was observed with rituximab in CD20+ models and with trastuzumab in HER2+ models. Stimulation with pegfilgrastim was associated with significant enhancement of leukocyte content in spleen as well as mobilization of activated monocytes/granulocytes from the spleen to the tumor bed. These results suggest that pegfilgrastim could constitute a potent adjuvant for immunotherapy with mAbs possessing ADCC/ADCP properties. Mol Cancer Ther; 15(6); 1238–47. ©2016 AACR.