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Potentiation of PD-L1 blockade with a potency-matched dual cytokine antibody-fusion protein leads to cancer eradication in BALB/c-derived tumors but not in other mouse strains 
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Reagents and tumor models characterization. (a) Schematic representation of the domain assembly of IL2-F8-TNFmut. (b) Microscopic fluorescence analysis of EDA expression on <t>CT26,</t> <t>WEHI-164,</t> <t>LLC</t> and F9 tumor sections detected with IL2-F8-TNFmut or IL2-KSF-TNFmut (green for anti-murine IL2, Alexa Fluor 488) and anti-CD31 (red, Alexa Fluor 594), 20x magnification, scale bars = 100µm.
Potentiation of PD-L1 blockade with a potency-matched dual cytokine antibody-fusion protein leads to cancer eradication in BALB/c-derived tumors but not in other mouse strains 
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Therapeutic performance of IL2-F8-TNFmut in combination with anti-PD-L1 treatment. Data represent mean tumor volume ± SEM. For all therapies mice were injected three times intravenously (black arrows) every 48 hours with either PBS, IL2-F8-TNFmut, 200μg anti-mouse PD-L1 or a combination of the two (IL2-F8-TNFmut six hours before anti-PD-L1 or the opposite). n = 5 mice per group (unless stated elsewhere), CR = complete response. (a) Therapy in Balb/c mice bearing CT26 colon carcinoma lesions. Treatment started when tumors reached a volume of 80 mm3, IL2-F8-TNFmut was dosed at 50µg. n = 5 mice per group, CR = complete response. (b) Tumor re-challenge study. After 37 days, mice with complete responses were injected subcutaneously with 4 x 106 CT26 cells in the flank. n= 5 for PBS group (n = 4 from day 12), n= 4 for re-challenge group. (c) Therapy in Balb/c mice <t>bearing</t> <t>WEHI-164</t> tumors. Treatment started when tumors reached a volume of 70 mm3, IL2-F8-TNFmut was dosed at 20µg. (d) Therapy in 129/SvEv mice bearing F9 teratocarcinomas. Treatment started when tumors reached a volume of 80 mm3, IL2-F8-TNFmut was dosed at 40µg. (e) Therapy in C57BL/6 mice bearing <t>LLC</t> tumors. Treatment started when tumors reached a volume of 70 mm3, IL2-F8-TNFmut was dosed at 40µg. n=4 from day 15 for groups IL2-F8-TNFmut + anti-PD-L1 and PBS, from day 16 for group anti-PD-L1 and from day 20 for groups anti-PD-L1 + IL2-F8-TNFmut and IL2-F8-TNFmut.
Potentiation of PD-L1 blockade with a potency-matched dual cytokine antibody-fusion protein leads to cancer eradication in BALB/c-derived tumors but not in other mouse strains 
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Microscopic analysis of therapeutic performance of Il2-F8-TNFmut in combination with anti-PD-L1 treatment. (a) Immunofluorescence analysis of tumor targeting properties of an anti-PD-L1 antibody 24 hours after IL2-F8-TNFmut + anti-PD-L1 treatment in mice <t>bearing</t> <t>CT26</t> or <t>LLC</t> lesions, cryosections were stained with anti-rat IgG (green, Alexa Fluor 488) and anti-CD31 (red, Alexa Fluor 594), 20x magnification, scale bars = 100µm. Immunofluorescence analysis of tumor infiltrating cells on CT26 (b) or LLC (c) tumor sections 24 hours after treatment with PBS or IL2-F8-TNFmut + anti-PD-L1, marker specific for NK cells (NCR1), CD4+ T cells (CD4), CD8+ T cells (CD8) and T regs (FoxP3) were stained in green (Alexa Fluor 488), anti-CD31 (red, Alexa Fluor 594), 20x magnification, scale bars = 100µm.
Potentiation of PD-L1 blockade with a potency-matched dual cytokine antibody-fusion protein leads to cancer eradication in BALB/c-derived tumors but not in other mouse strains Cancer immunology, immunotherapy : CII, 2018 Jul 04
"Reagents and tumor models characterization. (a) Schematic representation of the domain assembly of IL2-F8-TNFmut. (b) Microscopic fluorescence analysis of EDA expression on <t>CT26,</t> <t>WEHI-164,</t> <t>LLC</t> and F9 tumor sections detected with IL2-F8-TNFmut or IL2-KSF-TNFmut (green for anti-murine IL2, Alexa Fluor 488) and anti-CD31 (red, Alexa Fluor 594), 20x magnification, scale bars = 100µm. "
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