Anti-chemokin like receptor 1 antibodies and their therapeutic application
A humanized antibody and antibody technology, applied in the direction of antibodies, anti-receptors/cell surface antigens/cell surface determinants, immunoglobulins, anti-inflammatory agents, etc. Synthesis, difficulty in production, etc.
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Embodiment 1
[0423] Embodiment 1: DSS induces colitis
[0424] Colitis was induced in 8- to 10-week-old C57BI / 6 male mice for 6 days by adding 2% (w / v) DSS to sterile drinking water ad libitum. Treatment with intraperitoneal injection: isotype control hIgG1 (10 μg / mouse), RvE1 (1 μg / mouse) or 2G1 antibody (10 μg / mouse) three times a day for 5 days. Colitis follow-up parameters consisting of body weight and stool score (0: normal stool; 4: bloody stool) were performed daily. When mice were euthanized, the length of the colon, which indicated the severity of the pathology, was measured. Extinction indices under different conditions were determined as described by Bannenberg et al. (2005).
[0425] result: figure 2 The DSS animal model shown is an acute inflammation model. figure 1 showed that the overall state of animals treated with anti-CMKLR1 antibody was better than that of animals receiving control antibody or resolvin RvE1. Body weight loss of mice treated with anti-CMKLR1 ( fi...
Embodiment 2
[0426] Embodiment 2: TNBS induces colitis
[0427] On day 0, colitis was induced in 8- to 10-week-old C57BI / 6 male mice by intra-rectal injection of 200 μL of 5% haptenizing reagent TNBS in 50% ethanol. Intraperitoneal injection treatment: RvE1 (1 μg / mouse) once a day or 2G1 antibody (10 μg / mouse) twice a day for 3 days in total. Colitis follow-up parameters consisting of body weight and stool score (0: normal stool; 4: bloody stool) were performed daily (data not shown). After euthanasia of the mice, the length of the colon, which indicates the severity of the pathology, was measured.
[0428] Results: TNBS-induced colitis is another model of acute inflammation. image 3 showed that animals treated with anti-CMKLR1 or RvE1 had the same colon length as normal animals (wt). However, animals treated with isotype controls had shortened colon lengths. These results confirm that anti-CMKLR1 antibodies, like RvE1, have therapeutic potential in a mouse model of acute inflammation...
Embodiment 3
[0429] Example 3: IL-10KO Model - Spontaneous Colitis Model
[0430] Mainly due to lack of regulatory T cell function (through secretion of IL-10 in the gut), IL-10 KO mice develop spontaneous colitis from 20 weeks of age. IL-10KO mice were followed up 3 times a week from 18 weeks of age to maintain weight loss and stool consistency, which are clinical features of this pathology. Anti-CMKLR1 antibody (2G1) or isotype control (hIgG1) was injected intraperitoneally for 2 weeks (25 μg / injection, 3 times a week) when body weight loss exceeded 5% and stool score was higher than or equal to 1.
[0431] Results: A chronic inflammation model was used to study the efficacy of anti-CMKLR1 antibody treatment. Figure 4 Analysis of percent body weight loss when animals are treated with isotype control or anti-CMKLR1 antibody is shown ( Figure 4 A) and stool score ( Figure 4 B). Results showed that animals treated with anti-CMKLR1 antibodies lost less body weight and had better fecal...
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