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Characterization of ASKP1240, a fully human antibody targeting human CD40 with potent immunosuppressive effects.

Okimura K, Maeta K, Kobayashi N, Goto M, Kano N, Ishihara T, Ishikawa T, Tsumura H, Ueno A, Miyao Y, Sakuma S, Kinugasa F, Takahashi N, Miura T - Am. J. Transplant. (2014)

Bottom Line: In addition, ASKP1240 did not destabilize platelet thrombi under physiological high shear conditions while mouse anti-human CD154 mAb (mu5C8) did.And ASKP1240 itself did not activate platelet and endothelial cells.The immunosuppressive effect was well correlated with the CD40 receptor saturation.

View Article: PubMed Central - PubMed

Affiliation: Development Research Laboratories, Kyowa Hakko Kirin Co., Ltd., Shizuoka, Japan.

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Related in: MedlinePlus

Inhibition of DTH reactions and antibody productions in vivo. (A) Animals were immunized once with TTx on day 0 and challenged with injections into the thoracic skin of serially diluted TTx on day 21. ASKP1240 or placebo was administered intravenously on days 0, 7 and 14. At 48 h after challenge, skin reactions at the injection site were scored as described in the Materials and Methods section. The DTH scores are expressed as the mean ± SE of five individuals. (B, C) Animals were immunized once with TTx on day 0 and blood samples were obtained twice per week for serum titration. Anti-TTx IgG (B) and anti-TTx IgM (C) titers were measured by ELISA. The IgG and IgM titers are expressed as the means ± SE of five individuals. DTH, delayed-type hypersensitivity; ELISA, enzyme-linked immunosorbent assay; TTx, tetanus toxoid.
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fig04: Inhibition of DTH reactions and antibody productions in vivo. (A) Animals were immunized once with TTx on day 0 and challenged with injections into the thoracic skin of serially diluted TTx on day 21. ASKP1240 or placebo was administered intravenously on days 0, 7 and 14. At 48 h after challenge, skin reactions at the injection site were scored as described in the Materials and Methods section. The DTH scores are expressed as the mean ± SE of five individuals. (B, C) Animals were immunized once with TTx on day 0 and blood samples were obtained twice per week for serum titration. Anti-TTx IgG (B) and anti-TTx IgM (C) titers were measured by ELISA. The IgG and IgM titers are expressed as the means ± SE of five individuals. DTH, delayed-type hypersensitivity; ELISA, enzyme-linked immunosorbent assay; TTx, tetanus toxoid.

Mentions: The ASKP1240 inhibited DTH reaction in a dose-dependent manner (Figure 4A). Histopathologically, vasculitis and inflammatory cell infiltration including mononuclear cells and acidophils were observed in the dermis and subcutis at the challenge sites injected with TTx in the control group, but not at the sites injected with physiological saline. The incidences and degrees of histological changes decreased dose dependently (data not shown). Anti-TTx antibodies were also assessed over time, through day 23. ASKP1240 dose-dependently inhibited anti-TTx IgG and anti-TTx IgM productions (Figure 4B and C) with complete inhibition in antibody formation seen at doses of 10 mg/kg.


Characterization of ASKP1240, a fully human antibody targeting human CD40 with potent immunosuppressive effects.

Okimura K, Maeta K, Kobayashi N, Goto M, Kano N, Ishihara T, Ishikawa T, Tsumura H, Ueno A, Miyao Y, Sakuma S, Kinugasa F, Takahashi N, Miura T - Am. J. Transplant. (2014)

Inhibition of DTH reactions and antibody productions in vivo. (A) Animals were immunized once with TTx on day 0 and challenged with injections into the thoracic skin of serially diluted TTx on day 21. ASKP1240 or placebo was administered intravenously on days 0, 7 and 14. At 48 h after challenge, skin reactions at the injection site were scored as described in the Materials and Methods section. The DTH scores are expressed as the mean ± SE of five individuals. (B, C) Animals were immunized once with TTx on day 0 and blood samples were obtained twice per week for serum titration. Anti-TTx IgG (B) and anti-TTx IgM (C) titers were measured by ELISA. The IgG and IgM titers are expressed as the means ± SE of five individuals. DTH, delayed-type hypersensitivity; ELISA, enzyme-linked immunosorbent assay; TTx, tetanus toxoid.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4225473&req=5

fig04: Inhibition of DTH reactions and antibody productions in vivo. (A) Animals were immunized once with TTx on day 0 and challenged with injections into the thoracic skin of serially diluted TTx on day 21. ASKP1240 or placebo was administered intravenously on days 0, 7 and 14. At 48 h after challenge, skin reactions at the injection site were scored as described in the Materials and Methods section. The DTH scores are expressed as the mean ± SE of five individuals. (B, C) Animals were immunized once with TTx on day 0 and blood samples were obtained twice per week for serum titration. Anti-TTx IgG (B) and anti-TTx IgM (C) titers were measured by ELISA. The IgG and IgM titers are expressed as the means ± SE of five individuals. DTH, delayed-type hypersensitivity; ELISA, enzyme-linked immunosorbent assay; TTx, tetanus toxoid.
Mentions: The ASKP1240 inhibited DTH reaction in a dose-dependent manner (Figure 4A). Histopathologically, vasculitis and inflammatory cell infiltration including mononuclear cells and acidophils were observed in the dermis and subcutis at the challenge sites injected with TTx in the control group, but not at the sites injected with physiological saline. The incidences and degrees of histological changes decreased dose dependently (data not shown). Anti-TTx antibodies were also assessed over time, through day 23. ASKP1240 dose-dependently inhibited anti-TTx IgG and anti-TTx IgM productions (Figure 4B and C) with complete inhibition in antibody formation seen at doses of 10 mg/kg.

Bottom Line: In addition, ASKP1240 did not destabilize platelet thrombi under physiological high shear conditions while mouse anti-human CD154 mAb (mu5C8) did.And ASKP1240 itself did not activate platelet and endothelial cells.The immunosuppressive effect was well correlated with the CD40 receptor saturation.

View Article: PubMed Central - PubMed

Affiliation: Development Research Laboratories, Kyowa Hakko Kirin Co., Ltd., Shizuoka, Japan.

Show MeSH
Related in: MedlinePlus