Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Anti-cd70 antibody and its use for the treatment of cancer and immune disorders

an anti-cd70 antibody and immune disorder technology, applied in antibody medical ingredients, immunological disorders, metabolism disorders, etc., can solve the problems of significant adverse side effects and little treatment effect in established diseases

Inactive Publication Date: 2008-06-12
SEATTLE GENETICS INC
View PDF25 Cites 47 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention provides CD70 antibodies and other binding agents that can be used to treat CD70-expressing cancers and immunological disorders. These antibodies have a cytotoxic, cytostatic, or immunosuppressive effect on CD70-expressing cells in the absence of conjugation to a therapeutic agent. The antibodies can compete with monoclonal antibodies 1F6 and 2F2 for binding to CD70. The CD70-binding antibodies can be administered to a subject to treat a CD70-expressing cancer or an immunological disorder.

Problems solved by technology

However, such treatment had little efficacy in established disease.
However, these agents are not specific and cause significant adverse side effects.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Anti-cd70 antibody and its use for the treatment of cancer and immune disorders
  • Anti-cd70 antibody and its use for the treatment of cancer and immune disorders
  • Anti-cd70 antibody and its use for the treatment of cancer and immune disorders

Examples

Experimental program
Comparison scheme
Effect test

example 1

Construction of Chimeric Anti CD70 Antibody

[0188]To determine the cDNA sequences encoding the light (VL) and heavy (VH) chain variable regions of 1F6 and 2F2 mAb, total RNA was isolated from the 1F6 and 2F2 hybridomas using TRIzol® Reagent (Invitrogen, Carlsbad, Calif.) according to the manufacturer's instructions. Gene-specific primers mIgcK1: 5′-CTT CCA CTT GAC ATT GAT GTC TTT G-3′ (SEQ ID NO:41) and mIgG1: 5′-CAG GTC ACT GTC ACT GGC TCA G-3′ (SEQ ID NO:42) were applied to reverse transcribe the light chain variable (VL) and heavy chain variable (VH) first strand cDNAs from both RNA preparations, respectively. First strand cDNA reactions were run using the SuperScript™ First Strand Synthesis System for RT-PCR from Invitrogen. The VL and VH cDNAs were then poly-G tailed using terminal deoxynucleotidyl transferase (TdT) and the supplied TdT buffer, according to conditions specified by the manufacturer (Invitrogen). Poly-G tailed VL and VH first strand cDNAs were then subjected to PC...

example 2

Chimeric 1F6 Mediates ADCC Against CD70+ Tumor Cell Lines

[0202]The ability of c1F6 to mediate ADCC against the CD70+ cell lines WIL2-S, Caki-1 and 786-0 was measured using a standard 51Cr release assay. Tumor cells were labeled for one hour with 100 μCi Na251CrO4, washed thoroughly to remove unincorporated radioisotope, then plated in a 96-well plate at a concentration of 5,000 cells per well. Antibodies c1F6, m1F6 or human Ig were added to appropriate wells at a final concentration of 1 μg / ml for 0.5 hours prior to the addition of effector PBMC. PBMC were adjusted to reflect an effector cell to target cell ratio of 30 CD16+ cells:1 target cell. After 4 hours incubation, the 51Cr released from lysed cells was measured and the percent specific lysis calculated as {(test sample cpm−spontaneous cpm)÷(total cpm−spontaneous cpm)}×100. Spontaneous release of isotope was determined from the supernatant of target cells incubated in medium alone. Total counts were determined from target cell...

example 3

Chimeric 1F6-Coated Target Cells Recognized by PBMC from Multiple Donors

[0203]Caki-1 renal cell carcinoma cells were labeled with Na251CrO4, treated with graded doses of c1F6, and then incubated with effector PBMC from two normal donors. Specific lysis was assessed after 4 hours incubation as described in Example 2. Donor 2051661 and ND016 efficiently lysed Caki-1 target cells treated with 1 or 0.1 μg / ml c1F6 (FIG. 6). Specific lysis decreased in an antibody dose-dependent manner thereafter, and was negligible when target cells were treated with 0.001 μg / ml c1F6. Target cells mixed with non-binding control Ig (hIg) were not lysed by PBMC from either donor.

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

PropertyMeasurementUnit
pHaaaaaaaaaa
pHaaaaaaaaaa
concentrationaaaaaaaaaa
Login to View More

Abstract

Disclosed are CD70 binding agents, such as anti-CD70 antibodies and derivatives, that induce a cytotoxic, cytostatic or immunosuppressive without conjugation to a therapeutic agents, as well as pharmaceutical compositions and kits comprising the antibody or derivative. Also disclosed are methods for the treatment and prevention of CD70-expressing cancers and immunological disorders comprising administering to a subject the CD70-binding agent.

Description

CROSS REFERENCES TO RELATED APPLICATIONS[0001]This application is a Divisional of 11 / 251,173 filed Oct. 14, 2005, which claims the benefit of U.S. Provisional Patent Application No. 60 / 619,018 filed Oct. 15, 2004, and U.S. Provisional Application No. 60 / 645,355 filed Jan. 19, 2005, each of which is incorporated by reference herein in its entirety.BACKGROUND OF THE INVENTION[0002]CD70 is a member of the tumor necrosis factor (TNF) family of cell membrane-bound and secreted molecules that are expressed by a variety of normal and malignant cell types. The primary amino acid (AA) sequence of CD70 predicts a transmembrane type II protein with its carboxyl terminus exposed to the outside of cells and its amino terminus found in the cytosolic side of the plasma membrane (Bowman et al., 1994, J. Immunol. 152:1756-61; Goodwin et al., 1993, Cell 73:447-56). Human CD70 is composed of a 20 AA cytoplasmic domain, an 18 AA transmembrane domain, and a 155 AA extracytoplasmic domain with two potent...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(United States)
IPC IPC(8): A61K39/395C07K16/30
CPCA61K2039/505C07K16/2875C07K2317/734C07K2317/24C07K2317/732C07K2317/21A61P1/00A61P1/02A61P1/04A61P1/16A61P3/10A61P5/00A61P5/14A61P5/18A61P7/00A61P7/04A61P7/06A61P9/00A61P9/06A61P9/10A61P11/00A61P11/02A61P11/06A61P11/08A61P13/12A61P15/08A61P17/00A61P17/04A61P17/06A61P17/14A61P19/00A61P19/02A61P21/00A61P21/04A61P25/00A61P27/02A61P29/00A61P31/00A61P31/06A61P33/00A61P35/00A61P35/02A61P37/00A61P37/02A61P37/04A61P37/06A61P37/08A61P43/00
Inventor LAW, CHE-LEUNGMCEARCHERN, JULIEWAHL, ALAN F.
Owner SEATTLE GENETICS INC
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com