Basic Information
-
Gene Targeting Strategy
-
Exons 2-7 of the murine 4-1bb gene, which encodes the extracellular domain, was replaced by the human 4-1BB counterpart in B-h4-1BB/hCD40 mice. Exons 2-7 of the murine Cd40 gene, which encodes the extracellular domain, was replaced by human CD40 exons 2-7 in B-h4-1BB/hCD40 mice.
-
Protein Expression Analysis
-
Species-specific CD40 and 4-1BB expression analysis in double humanized B-h4-1BB/hCD40 mice. Following anti-CD3ε stimulation in vivo, splenocytes were collected from wild-type C57BL/6 (+/+) and homozygous B-h4-1BB/hCD40 (H/H) mice and analyzed by flow cytometry using species-specific anti-CD40 anti-4-1BB antibodies. Human CD40 and 4-1BB were exclusively detected in B-h4-1BB/hCD40 mice compared to wild-type mice. -
In Vivo Efficacy Studies
-
Antitumor activity of anti-human 4-1BB and anti-human CD40 antibodies in double humanized B-h4-1BB/hCD40 mice. Murine colon cancer MC38 cells were subcutaneously implanted into homozygous B-h4-1BB/hCD40 mice (female, 6-8-week-old, n=5). Mice were grouped when tumor volume reached approximately 400 mm3, at which time they were treated with h4-1BB and hCD40 antibodies. (A) Combination therapy of anti-human 4-1BB and anti-human CD40 antibodies (in house) significantly inhibited MC38 tumor growth in B-h4-1BB/hCD40 mice, (B) without negatively impacting body weight changes. Altogether, B-h4-1BB/hCD40 mice provide a powerful preclinical model for in vivo evaluation of anti-human 4-1BB and CD40 antibodies. Values are expressed as mean ± SEM.
