Utility of epirubicin-incorporating micelles tagged with anti-tissue factor antibody clone with no anticoagulant effect.
Bottom Line: In vitro, all forms of anti-TF1859-NC-6300 showed higher cytocidal effects than NC-6300 in BxPC3, whereas this enhanced effect was not observed in SUIT2.Likewise, all forms of anti-TF1859-NC-6300 significantly suppressed tumor growth when compared to NC-6300 in the BxPC3, but not in the SUIT2, xenograft model.Thus, we have confirmed an enhanced antitumor effect of anti-TF1859-NC-6300 in a TF-high expressing tumor; anti-TF1859-IgG-NC-6300 could be used to simplify the manufacturing process of the antibody-micelle conjugation for future clinical studies.
Affiliation: Division of Developmental Therapeutics, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Japan.Show MeSH
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Mentions: The antitumor activities of anti‐TF1859‐IgG‐NC‐6300, anti‐TF1859‐F(ab’)2‐NC‐6300, and anti‐TF1859‐Fab’‐NC‐6300 exceeded that of NC‐6300 in the BxPC3 xenograft models (P = 0.021, P < 0.001, P < 0.001, respectively; Fig. 3a). Among anti‐TF1859‐NC‐6300, anti‐TF1859‐IgG‐NC‐6300 versus anti‐TF1859‐F(ab’)2‐NC6300 and anti‐TF1859‐F(ab’)2‐NC‐6300 versus anti‐TF1859‐Fab’‐NC‐6300 were not significant. Anti‐TF1859‐IgG‐NC‐6300 was superior to anti‐TF1859‐Fab’‐NC‐6300 (P = 0.002). In contrast, in SUIT2 xenografts, anti‐TF1859‐IgG‐NC‐6300, anti‐TF1859‐F(ab’)2‐NC‐6300, and anti‐TF1859‐Fab’‐NC‐6300 were all equivalent to NC‐6300 (Fig. 3c). There were no treatment‐related deaths. No significant body weight loss was observed among any of the anti‐TF1859‐NC‐6300 groups, NC‐6300 groups, or control groups. However, the free epirubicin administration groups showed significant body weight loss compared with all the other groups in both BxPC3 and SUIT2 models (Fig. 3b,d).
Affiliation: Division of Developmental Therapeutics, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Japan.