B-hOX40 mice

Basic Information

Targeting strategy

Gene targeting strategy for B-hOX40 mice. The exons 1-5 of mouse Tnfrsf4 gene that encode the extracellular domain were replaced by human TTNFRSF4 exons 1-5 in B-hOX40 mice.

mRNA expression analysis

Species-specific OX40 gene expression analysis in wild-type and humanized B-hOX40 mice by RT-PCR. Murine Ox40 mRNA was detected in splenocytes isolated from wild-type (+/+) mice, while human OX40 mRNA was exclusively detected in homozygous B-hOX40 (H/H) mice.

Protein expression analysis

Species-specific OX40 protein expression analysis in humanized B-hOX40 mice. Splenocytes were isolated from wild-type C57BL/6 (+/+) and homozygous B-hOX40 (H/H) mice and analyzed by flow cytometry using species-specific anti-OX40 antibodies. Murine OX40 protein was detected in wild-type mice, while human OX40 protein was exclusively detected in B-hOX40 mice.

In vivo efficacy evaluation of anti-human OX40 antibodies

Antitumor activity of an anti-human OX40 antibody in humanized B-hOX40 mice. Murine colon cancer MC38 cells (5ⅹ10⁵) were subcutaneously implanted into homozygous B-hOX40 mice (male, 4-6 week-old, n=5). Mice were grouped when tumor volume reached approximately 100 mm³, at which time they were treated with an anti-human OX40 antibody at schedules indicated. (A) The anti-human OX40 antibody inhibited MC38 tumor growth in B-hOX40 mice, (B) without negatively impacting body weight changes. This data demonstrates that B-hOX40 mice are a powerful preclinical model for in vivo evaluation of anti-human OX40 antibodies. Values are expressed as mean ± SEM.

 

Antitumor activity of an anti-human OX40 antibody (MOXR0916, in house) in humanized B-hOX40 mice. Murine colon cancer MC38 cells (5ⅹ10⁵) were subcutaneously implanted into homozygous B-hOX40 mice (female, 4-6 week-old, n=6). Mice were grouped when tumor volume reached approximately 150±50 mm³, at which time they were treated with different doses of MOXR0916 at schedules indicated. (A) High dose of MOXR0916 inhibited MC38 tumor growth in B-hOX40 mice, (B) without negatively impacting body weight changes. This data demonstrates that B-hOX40 mice are a powerful preclinical model for in vivo evaluation of anti-human OX40 antibodies. Values are expressed as mean ± SEM.

References

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