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Combination therapy of an afucosylated CD20 antibody with bendamustine

A technology of fucosylation and bendamustine, applied in the direction of antibody medical components, antibodies, chemical instruments and methods, etc.

Inactive Publication Date: 2012-07-18
ROCHE GLYCART AG
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

CD20 is expressed on greater than 90% of B-cell non-Hodgkin's lymphomas (NHL) (Anderson, K.C. et al., Blood 63 (1984) 1424-1433)), but is expressed on hematopoietic stem cells, pro-B cells, normal Not found in plasma cells, or other normal tissues (Tedder, T.F. et al., J, Immunol. 135(2)(1985)973-979)

Method used

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  • Combination therapy of an afucosylated CD20 antibody with bendamustine
  • Combination therapy of an afucosylated CD20 antibody with bendamustine
  • Combination therapy of an afucosylated CD20 antibody with bendamustine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment

[0131] Experimental protocol

[0132] Antitumor activity of combination therapy with type II anti-CD20 antibody (B-HH6-B-KV1GE) and bendamustine

[0133] test agent

[0134] Afucosylated anti-CD20 antibody B-HH6-B-KV1 GE (afucosylated humanized B-Ly1, glycoengineered B-HH6-B-KV1, see WO 2005 / 044859 and WO 2007 / 031875) are provided as stock solutions (9.4 mg / ml) from GlycArt, Schlieren, Switzerland. Antibody buffer contains histidine, trehalose and polysorbate 20. Antibody solutions were appropriately diluted in PBS from stock for prior injection.

[0135] Clinical grade rituximab (Mabthera) was obtained from Hoffmann La Roche, Basel.

[0136] Bendamustine (Ribomustin ) was purchased from Mundipharma GmbH, Limburg an der Lahn, Germany. The required dilutions were adjusted from the 25 mg / ml stock solution made.

[0137] Cell Lines and Culture Conditions

[0138] The human Z138 mantle cell lymphoma cell line was routinely cultured in DMEM supplemented with 10% feta...

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Abstract

The present invention is directed to the combination therapy of an afucosylated anti-CD20 antibody with bendamustine for the treatment of cancer, especially to the combination therapy of CD20 expressing cancers with an afucosylated humanized B-Ly1 antibody and bendamustine.

Description

[0001] The present invention relates to the combination therapy of afucosylated CD20 antibody and bendamustine for treating cancer. Background of the invention [0002] Afucosylated Antibodies [0003] The cell-mediated effector functions of monoclonal antibodies can be enhanced by engineering their oligosaccharide components, as documented in P. et al., Nature Biotechnol. 17(1999) 176-180 and US 6,602,684. IgG1 type antibodies (ie, the antibodies most commonly used in cancer immunotherapy) are glycoproteins with a conserved N-linked glycosylation site at Asn297 in each CH2 domain. Two complex biantennary oligosaccharides attached to Asn297 are buried between each CH2 domain, forming extensive contacts with the polypeptide backbone, and their presence is essential for antibody-mediated effector functions such as antibody-dependent cellular cytotoxicity (ADCC). Important (Lifely, M.R. et al., Glycobiology 5 (1995) 813-822; Jefferis, R. et al., Immunol. Rev. 163 (1998) 59-76;...

Claims

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Application Information

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IPC IPC(8): A61K39/395C07K16/28A61K31/4184A61P35/00
CPCA61K39/39558A61K45/06A61K2039/505C07K2317/41C07K16/2887A61K31/4184C07K2317/24A61K2300/00A61P35/00A61K39/395C07K16/28
Inventor F.赫廷C.克莱恩
Owner ROCHE GLYCART AG
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