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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

Cytotoxic assay of ASKP1240. Antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) activities of 100 µg/mL of antibodies were evaluated by chromium release assay. The percentage of specific lysis of B-lymphoma cells (Raji) is represented as the mean ± SD of three wells.
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fig01: Cytotoxic assay of ASKP1240. Antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) activities of 100 µg/mL of antibodies were evaluated by chromium release assay. The percentage of specific lysis of B-lymphoma cells (Raji) is represented as the mean ± SD of three wells.

Mentions: The constant region of ASKP1240 is converted to IgG4 to reduce ADCC and CDC activities that might injure CD40 positive cells (i.e. B cells, monocytes, platelet, endothelial cells, etc.). One hundred micrograms per milliliter of ASKP1240 IgG4 did not induce CD40 expressing cell lysis via ADCC and CDC activity in contrast with rituximab and IgG1 version of ASKP1240 (Figure 1).


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)

Cytotoxic assay of ASKP1240. Antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) activities of 100 µg/mL of antibodies were evaluated by chromium release assay. The percentage of specific lysis of B-lymphoma cells (Raji) is represented as the mean ± SD of three wells.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig01: Cytotoxic assay of ASKP1240. Antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) activities of 100 µg/mL of antibodies were evaluated by chromium release assay. The percentage of specific lysis of B-lymphoma cells (Raji) is represented as the mean ± SD of three wells.
Mentions: The constant region of ASKP1240 is converted to IgG4 to reduce ADCC and CDC activities that might injure CD40 positive cells (i.e. B cells, monocytes, platelet, endothelial cells, etc.). One hundred micrograms per milliliter of ASKP1240 IgG4 did not induce CD40 expressing cell lysis via ADCC and CDC activity in contrast with rituximab and IgG1 version of ASKP1240 (Figure 1).

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