Figure 3
Figure 3. CC-122 reduces tumor growth and promotes degradation of Aiolos and Ikaros in vivo and in DLBCL patients. (A) CB-17 SCID mice with OCI-LY10 xenograft tumors were treated with either vehicle or 3 or 30 mg/kg CC-122 daily. The average tumor volume of each group (n = 10) ± standard deviation (SD) is shown as a function of time. *P = .028; ***P < .001 unpaired Student t test. (B) CB-17 SCID mice with WSU-DLCL2 xenograft tumors were treated with either vehicle or 30 mg/kg CC-122 daily. The average tumor volume of each group (n = 10) ± SD is shown as a function of time. **P < .01 unpaired Student t test. (C and D) WSU-DLCL2 xenograft tumor samples were harvested at indicated time points after final dosing with either vehicle or CC-122 (30 mg/kg). Tissues were then subjected to FFPE IHC for Aiolos and Ikaros. Graphical representation of Aiolos and Ikaros degradation (mean ± SEM). *P < .01; **P < .001 1-way analysis of variance followed by Dunnett’s multiple comparison test. (E) Representative fields of DLBCL formalin fixed paraffin embedded (FFPE) samples stained with hematoxylin and eosin (H&E), CRBN, Aiolos, Ikaros, and IRF4. (F) Representative fields of FFPE samples from GCB R/R-DLBCL patients administered with 3 mg of CC-122 daily. Screening and cycle 1 day 15 biopsies were immunohistochemically stained with Aiolos, Ikaros, and CRBN antibodies as indicated.

CC-122 reduces tumor growth and promotes degradation of Aiolos and Ikaros in vivo and in DLBCL patients. (A) CB-17 SCID mice with OCI-LY10 xenograft tumors were treated with either vehicle or 3 or 30 mg/kg CC-122 daily. The average tumor volume of each group (n = 10) ± standard deviation (SD) is shown as a function of time. *P = .028; ***P < .001 unpaired Student t test. (B) CB-17 SCID mice with WSU-DLCL2 xenograft tumors were treated with either vehicle or 30 mg/kg CC-122 daily. The average tumor volume of each group (n = 10) ± SD is shown as a function of time. **P < .01 unpaired Student t test. (C and D) WSU-DLCL2 xenograft tumor samples were harvested at indicated time points after final dosing with either vehicle or CC-122 (30 mg/kg). Tissues were then subjected to FFPE IHC for Aiolos and Ikaros. Graphical representation of Aiolos and Ikaros degradation (mean ± SEM). *P < .01; **P < .001 1-way analysis of variance followed by Dunnett’s multiple comparison test. (E) Representative fields of DLBCL formalin fixed paraffin embedded (FFPE) samples stained with hematoxylin and eosin (H&E), CRBN, Aiolos, Ikaros, and IRF4. (F) Representative fields of FFPE samples from GCB R/R-DLBCL patients administered with 3 mg of CC-122 daily. Screening and cycle 1 day 15 biopsies were immunohistochemically stained with Aiolos, Ikaros, and CRBN antibodies as indicated.

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