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Combined therapy using vascular endothelial growth factor receptor antagonist for inhibiting growth of tumor

A vascular endothelium and antagonist technology, which is applied in the field of combined therapy for inhibiting tumor growth with vascular endothelial growth factor receptor antagonists, can solve the problems of low expression levels of VEGF ligands and their receptors, etc.

Inactive Publication Date: 2009-07-08
IMCLONE SYSTEMS
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] Although VEGF ligands are upregulated in tumor cells and their receptors are also upregulated in tumor-infiltrating vascular endothelial cells, VEGF ligands and their receptors are expressed at low levels in normal cells not associated with angiogenesis

Method used

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  • Combined therapy using vascular endothelial growth factor receptor antagonist for inhibiting growth of tumor
  • Combined therapy using vascular endothelial growth factor receptor antagonist for inhibiting growth of tumor
  • Combined therapy using vascular endothelial growth factor receptor antagonist for inhibiting growth of tumor

Examples

Experimental program
Comparison scheme
Effect test

Embodiment VIII

[0038] The VEGF receptor antagonist is before, during, or after starting chemotherapy or radiotherapy, and any combination thereof, i.e., before and during, before and after, during and after, or before starting chemotherapy and / or radiotherapy, During, and after giving. For example, when the VEGF receptor antagonist is an antibody, the antibody is usually administered between 1-30 days, preferably 3-20 days, more preferably 5-12 days before the start of radiotherapy and / or chemotherapy.

[0039] radiotherapy

[0040] The radiation source used in conjunction with the VEGF receptor antagonist may be extrinsic or intrinsic to the patient being treated. When the radiation source is external to the patient, the therapy is called external beam radiation therapy (EBRT). When the source of radiation is internal to the patient, the therapy is called brachytherapy (BT).

[0041] Radiation therapy is administered according to well-known standard techniques, using standard equipment m...

Embodiment 1

[0181] Example 1. Cell lines and media

[0182] NIH 3T3 cells were obtained from the American Type Culture Collection (Rockville MD). The C441 cell line was constructed by transfecting 3T3 cells with chimeric receptor mouse flk-1(VEGFR-2) / human fms. 10A2, a 3T3 transfectant containing the chimeric receptor human fms / mouse FLK-2, has been isolated and characterized (Dosil et al., Mol. Cell. Biol. 13:6572-6585 (1993)). Cells were typically maintained in Dulbecco's Modified Eagle's Medium (DME) supplemented with 10% calf serum (CS), 1 mM L-glutamine, antibiotics, and 600 μg / ml G418 (Geneticin; Sigma, St Louis MO).

[0183] The glioblastoma cell line, GBM-18, was maintained in DME supplemented with 5% calf serum, 1 mM L-glutamine, and antibiotics.

[0184] A stable 3T3 line secreting a soluble chimeric protein, mouse flk-1(VEGFR-2):SEAPs (secreted alkaline phosphatases) was produced and maintained in DMEM and 10% calf serum. Conditioned medium was collected. Isolation of solub...

Embodiment II

[0185] Example II. Isolation of Monoclonal Antibodies

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Abstract

The invention relates to a combination therapy for restraining tumor growth by vascular endothelial growth factor receptor antagonist. Concretely, the invention provides a method for alleviating or restraining the tumor growth of the mammal. The method comprises the step of combining the therapeutically effective dose of VEGF receptor antagonist with radiation treatment, chemotherapy and / or other receptor antagonists to treating the mammal.

Description

[0001] This application is a divisional application of the Chinese patent application 02809226.0 "Combined Therapy for Inhibiting Tumor Growth with Vascular Endothelial Growth Factor Receptor Antagonist" filed on March 4, 2002. [0002] This application is a continuation-in-part of application No. 09 / 798,689 filed March 2, 2001, which is a pending application No. 09 / 401,163 filed September 22, 1999 Continuation, Application No. 09 / 401,163 is a continuation-in-part of Application No. 08 / 967,113, filed November 10, 1997, Application No. 08 / 967,113 is a part of Patent No. 5,861,499, filed September 3, 1996 Continuation, Patent No. 5,861,499 is a continuation-in-part of Application No. 08 / 476,533 filed June 7, 1995, Application No. 08 / 476,533 is a continuation-in-part of Patent No. 5,840,301 filed October 20, 1994 , Patent No. 5,840,301 is an abandoned, continuation-in-part application No. 08 / 196,041 filed on February 10, 1994. The entire contents of the aforementioned prior applic...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/06A61K39/395A61P35/00
Inventor 帕特里夏·罗克韦尔尼尔I·戈尔茨坦
Owner IMCLONE SYSTEMS