Basic Information
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Details
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mRNA expression analysis
CCR8 gene expression in C57BL/6 and B-hCCR8 mice by RT-PCR. Mouse Ccr8 mRNA was detectable in thymocytes of wild-type mice (+/+) . Human CCR8 mRNA was detectable only in homozygous B-hCCR8 mice (H/H) but not in wild-type mice (+/+).
Protein expression analysis
Human CCR8 expression in B-hCCR8 mice. MC38 tumor cells were inoculated into wild-type C57BL/6 (+/+) and homozygous B-hCCR8 mice (H/H). Tumors were harvested at the endpoint of experiment, and tumor-infiltrating lymphocytes were analyzed by flow cytometry. Human CCR8 was detected on CD4+ T cells and Treg cells in tumors from homozygous B-hCCR8 mice, while mouse CCR8 was detected only in wild-type mice.
Tissue distribution of CCR8+ T lymphocytes in wildtype and B-hCCR8 mice bearing tumors. Human CCR8 was detected on CD4+ T cells and Treg cells in tumors isolated from homozygous B-hCCR8 mice, but not those T cells isolated from spleen or blood. Similarly, mouse CCR8 was detected in tumors and expressed on some T cells isolated from wild-type mice, but not on blood cells.
In vivo efficacy
Antitumor activity of anti-human CCR8 antibody in male B-hCCR8 mice
(A) Murine colon cancer MC38 cells were subcutaneously implanted into homozygous B-hCCR8 mice (male, 6-7 week-old, n=6). Mice were grouped when tumor volume reached approximately 100 mm3, at which time they were treated with anti-human CCR8 antibodies as indicated. (B) Body weight changes during treatment. As shown in panel A, anti-human CCR8 antibodies blunted tumor growth. Values are expressed as mean ± SEM.
Antitumor activity of anti-human CCR8 antibody in female B-hCCR8 mice
(A) Anti-human CCR8 antibody inhibited MC38 tumor growth in B-hCCR8 mice. Murine colon cancer MC38 cells were subcutaneously implanted into homozygous B-hCCR8 mice (female, 8 week-old, n=8). Mice were grouped when tumor volume reached approximately 100 mm3, at which time they were treated with anti-human CCR8 antibody as indicated. (B) Body weight changes during treatment. As shown in panel A, anti-human CCR8 antibody blunted tumor growth in B-hCCR8 mice. Values are expressed as mean ± SEM.
