Combination therapy of an afucosylated CD20 antibody with fludarabine and/or mitoxantrone

A technology of fucosylation and fucose content, which is applied in the direction of antibody medical components, chemical instruments and methods, anti-animal/human immunoglobulin, etc., can solve the problem of not being found

Inactive Publication Date: 2012-05-23
ROCHE GLYCART AG
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

CD20 is expressed on more 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 on plasma cells, or other normal tissues (Tedder, T.F. et al., J, Immunol. 135 (1985) 973-979)

Method used

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  • Combination therapy of an afucosylated CD20 antibody with fludarabine and/or mitoxantrone
  • Combination therapy of an afucosylated CD20 antibody with fludarabine and/or mitoxantrone
  • Combination therapy of an afucosylated CD20 antibody with fludarabine and/or mitoxantrone

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0155] Embodiment 1 (see figure 1 )

[0156] In vivo antitumor activity of combination therapy with afucosylated type II anti-CD20 antibody (B-HH6-B-KV1GE) and fludarabine

[0157] test agent

[0158] Type II anti-CD20 antibody B-HH6-B-KV1 GE (=humanized B-Ly1, glycoengineered B-HH6-B-KV1, see WO2005 / 044859 and WO2007 / 031875) was obtained from GlycArt, Schlieren, Stock solutions in Switzerland (c=9.4 mg / ml) are provided. Antibody buffer contains histidine, trehalose and polysorbate 20. Antibody solutions were appropriately diluted in PBS from stock for prior injection.

[0159] Fludarabine phosphate (Fludarabinmedac) was purchased from medac, Gesellschaft für klinische Spezialpraparate mbH, Fehlandstr. 3, 20354 Hamburg, Germany. The required dilutions were adjusted from the 25 mg / ml stock solution made.

[0160] Cell Lines and Culture Conditions

[0161] The human Z138 mantle cell lymphoma cell line was incubated in DMEM supplemented with 10% fetal calf serum (PAA Lab...

Embodiment 2

[0172] Embodiment 2 (see Figures 2 to 5 )

[0173] In Vitro Evaluation of the Antiproliferative Activity of an Afucosylated Type II Anti-CD20 Antibody (B-HH6-B-KV1 GE) with Fludarabine or Mitoxantrone

[0174] Materials and methods

[0175] Characterization of Applied Tumor Cell Lines

[0176] The following non-Hodgkin lymphoma (NHL) cell lines were used in the experiments: Granta-519, HBL-2, Rec-1, and Z-138 as mantle cell lymphoma cell lines and Karpas-422 as diffuse large B-cell lymphoma cell lines tumor cell lines. All cell lines were obtained from "Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH" (DSMZ), Braunschweig, Germany.

[0177] Cell Culture Conditions:

[0178] All cell lines were stored according to standard protocols and stored at 37°C, 5% CO 2 and 95% relative humidity in CO 2 cultured in an incubator. Granta 519, HBL-2, JeKo-1, Rec-1 and Z-138 were cultured in RPMI-1640 medium with 10% heat-inactivated FCS and 1% penicillin / streptomycin....

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Abstract

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

Description

[0001] The present invention relates to the combination therapy of afucosylated CD20 antibody and fludarabine and / or mitoxantrone 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 US6,602,684. 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...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/395C07K16/28A61P35/00A61K31/70A61K31/137
CPCA61K31/675A61K31/137A61K31/7076A61K39/39558A61K2039/505C07K2317/41C07K16/2887C07K2317/24A61K31/136A61K31/661A61P35/00A61P35/02A61P43/00A61K2300/00A61K31/70A61K39/395C07K16/28A61K39/3955A61K45/06C07K2317/73
Inventor M.德雷林D.A.海因里希F.赫廷C.克莱恩
Owner ROCHE GLYCART AG
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