Cancerous disease modifying antibodies

A technology of antibodies and chimeric antibodies, applied in allergic diseases, antibodies, radioactive carriers, etc., can solve problems such as insufficient cancer

A technology of antibodies and chimeric antibodies, applied in allergic diseases, antibodies, radioactive carriers, etc., can solve problems such as insufficient cancer

CN101622341AInactive Publication Date: 2010-01-06F HOFFMANN LA ROCHE & CO AG

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  • Cancerous disease modifying antibodies
  • Cancerous disease modifying antibodies
  • Cancerous disease modifying antibodies

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0127] Hybridoma production----hybridoma cell line AR90A56.11

[0128] According to the Budapest Treaty, the hybridoma cell line AR90A56.11 was deposited in the International Depository of Canada (the International Depository Authority of Canada, IDAC) on December 5, 2006, and the Bureau of Microbiology, Health Canada (Bureau of Microbiology, HealthCanada) (Canada, Ma 1015 Arlington Street, Winnipeg, Nitoba, R3E 3R2) with accession number 051206-03. Pursuant to 37 CFR 1.808, the depositor warrants that, at the time of grant of the patent, all constraints imposed on the public availability of the deposited material are irrevocable. If the depositary cannot release a viable sample, replace the deposit.

[0129] To generate hybridomas producing anticancer antibody AR90A56.11, single cell suspensions of frozen lung adenocarcinoma tumor tissue (Genomics Collaborative, Cambridge, MA) were prepared in PBS. Prepare IMMUNEASY by mixing gently TM(Qiagen, Venlo, The Netherlands) adjuv...

Embodiment 2

[0136] in vitro binding

[0137] AR90A56.11 monoclonal antibody was produced by growing hybridomas in CL-1000 flasks (BD Biosciences, Oakville, ON), harvested and reseeded twice / week. Standard antibody purification steps were followed using Protein G Sepharose 4 Fast Flow (Amersham Biosciences, Baie d'Urfe, QC). It is within the scope of the invention to use deimmunized, humanized, chimeric or murine monoclonal antibodies.

[0138] Association of AR90A56.11 with lung (A549, NCI-H23, NCI-H322M, NCI-H460, and NCI-H520), colon (Lovo), breast (MDA-MB-231), pancreas, Combination of (BxPC-3), prostate (PC-3) and ovarian (OVCAR-3) carcinomas, and non-cancer cell lines from skin (CCD-27sk) and lung (Hs888.Lu). All cell lines, except the lung cancer cell line NCI-H322M, were obtained from the American Type Tissue Collection (ATCC, Manassas, VA). NCI-H322M was obtained from the NCI-Frederick Cancer DCTD Tumor / Cell Line Repository (Frederick, MD).

[0139] By initially using DPBS (Ca...

Embodiment 3

[0142] In vivo tumor experiments using BxPC-3 cells

[0143] Examples 1 and 2 demonstrate that AR90A56.11 has anticancer properties against human cancer cell lines with detectable binding to several different cancer indicators. refer to Figure 4 and 5 , 8-10 week old female SCID mice were implanted with 5 million human pancreatic cells (BxPC-3) in 100 microliters of PBS solution by subcutaneous injection at the nape of the neck. The mice were randomly divided into two treatment groups, 8 in each group. On the day after implantation, in a solution containing 2.7mM KCl, 1mM KH 2 PO 4 , 137mM NaCl and 20mM Na 2 HPO 4 After dilution of the diluent from the stock concentrate, each group was administered intraperitoneally with 10 mg / kg AR90A56.11 detection antibody or buffer control in a volume of 300 microliters. The antibodies and control samples were then administered in the same manner 3 times per week for the duration of the study. Tumor growth was measured approximate...

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Abstract

The present invention relates to a method for producing cancerous disease modifying antibodies using a novel paradigm of screening. By segregating the anti-cancer antibodies using cancer cell cytotoxicity as an end point, the process makes possible the production of anti-cancer antibodies for therapeutic and diagnostic purposes. The antibodies can be used in aid of staging and diagnosis of a cancer, and can be used to treat primary tumors and tumor metastases. The anti-cancer antibodies can be conjugated to toxins, enzymes, radioactive compounds, cytokines, interferons, target or reporter moieties and hematogenous cells.

Description

field of invention [0001] The present invention relates to the isolation and production of cancerous disease-modifying antibodies (CDMABs) and to the use of these CDMABs alone or in combination with one or more CDMAB / chemotherapy agents in therapeutic and diagnostic procedures. The invention also relates to binding assay methods using the CDMABs of the invention. Background of the invention [0002] Monoclonal Antibodies as Cancer Therapy: Every individual with cancer is unique and different from other cancers, as is an individual's identity. Beyond that, current treatments treat all patients with the same type of cancer at the same stage in the same way. At least 30% of these patients will fail first-line therapy, thereby leading to subsequent rounds of therapy and an increased likelihood of treatment failure, metastasis, and ultimately death. A better treatment would be one that is tailored to the specific individual. Currently the only treatment that is itself tailor-m...

Claims

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Application Information

Patent Timeline
06 Jan 2010
Publication
CN101622341A
IPC
C12N5/18; C07K16/30; A61K39/395; C07K16/46; A61K47/48; C07K19/00; A61K51/10; C12N5/16; A61P35/00; C12P21/08; A61P37/04; G01N33/574; C07K16/18; G01N33/577
CPC
A61K47/4843; G01N33/5017; A61K47/48569; A61K2039/505; G01N33/57492; A61K47/48423; A61K51/1045; C07K16/30
Inventors
戴维·S·F·扬; 海伦·P·芬德利