Antibodies for cancer therapy and diagnosis

a cancer and antibody technology, applied in the field of antibodies for cancer therapy and diagnosis, can solve the problems of interfering with clinical utility, proving difficult to panning cellular targets with antibody phage,

Inactive Publication Date: 2008-07-10
CARTER PAUL J +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

This approach allows for the development of antibodies with high tumor selectivity and affinity for DAF, enabling effective treatment of lung cancer by selectively targeting cancer cells while minimizing impact on normal cells.

Problems solved by technology

Unfortunately tumor-binding antibodies obtained in this way often cross-react with many normal cells, which may interfere with their clinical utility.
In contrast, panning cellular targets with antibody phage has proved much more difficult because of the much lower effective antigen concentration, greater antigen complexity and the tendency of phage to bind non-specifically to cells.

Method used

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  • Antibodies for cancer therapy and diagnosis
  • Antibodies for cancer therapy and diagnosis
  • Antibodies for cancer therapy and diagnosis

Examples

Experimental program
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example 1

[0170]In the present example, a large naïve human single chain (sc) Fv phage library was used to search for tumor-associated antigens by panning with a lung adenocarcinoma cell line, 1264, and counter-selecting with a non-tumor bronchial epithelial cell line, BEAS-213. After 3 rounds of subtractive panning, 239 out of 673 clones analyzed, bound selectively to 1264 tumor cells in a phage ELISA. Diversity analysis of these tumor-selective clones by BstNI fingerprinting and nucleotide sequencing revealed 14 distinct scFv fragments. Four clones bound selectively to 1264 over BEAS-2B cells when analyzed by a more discriminating flow cytometric assay using scFv. Moreover, these clones showed only limited cross-reactivity to several primary human cell lines. One clone, LU30, also cross-reacted strongly with the lung adenocarcinoma line, A549. The LU30 antigen was identified as decay-accelerating factor (DAF, CD55) by expression cloning from a 1264 cDNA library. The mean number of DAF molec...

example 2

[0197]This Example describes how one may treat a human patient with lung cancer with a human antibody as described herein.

[0198]The VH and VL domains of the human antibody LU30 identified as described in the previous Example are joined to human IgG1 constant domains to generate an intact antibody with effector functions in vivo. The antibody may be expressed in a Chinese Hamster Ovary (CHO) cell (U.S. Pat. No. 4,816,567, expressly incorporated herein by reference). The recombinant antibody is recovered from the CHO cells and formulated as a lyophilized preparation which can be reconstituted with bacteriostatic water for injection (BWFI) to generate a reconstituted formulation for intravenous or subcutaneous administration to a human patient (see WO 97 / 04801). The reconstituted formulation is administered to a human patient diagnosed as having lung cancer, e.g. in an initial loading dose of about 4 mg / kg IV followed by weekly doses of about 2 mg / kg IV. Candidate patients for therapy ...

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Abstract

The present application describes a method for making antibodies which can be used for cancer diagnosis or therapy. The application also discloses a method for identifying an antigen which is differentially expressed on the surface of two or more distinct cell populations. The application additionally describes human antibodies directed against decay accelerating factor (DAF), as well as therapeutic compositions comprising such antibodies. Moreover, the application discloses a method of treating lung cancer with antibodies directed against DAF.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]This application is a continuation application of co-pending U.S. application Ser. No. 10 / 447,331, filed on May 28, 2003, which is a divisional application of Ser. No. 09 / 515,825, filed on Feb. 29, 2000, incorporated herein by reference, and to which priority is claimed under 35 U.S.C. § 120, which co-pending application is a non-provisional application filed under 37 C.F.R. 1.53(b)(1) which claims priority under 35 U.S.C. 119(e) to provisional application No. 60 / 122,262 filed Mar. 1, 1999, the contents of which are incorporated herein by reference.BACKGROUND OF THE INVENTION[0002]1. Field of the Invention[0003]The present invention concerns a method for making antibodies which can, for example, be used for cancer diagnosis or therapy. The invention further provides a method for identifying an antigen which is differentially expressed on the surface of distinct cell populations. The present invention additionally provides human antibodies...

Claims

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Application Information

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Patent Type & AuthorityApplications(United States)
IPC IPC(8): C12Q1/70C07K16/30A61K38/00G01N33/574A61K39/395C07K16/00C07K16/28
CPCA61K38/00A61K39/39541A61K2039/505C07K16/2896C07K2317/622C07K2317/21A61K2300/00
InventorCARTER, PAUL J.RIDGWAY, JOHN B.
OwnerCARTER PAUL J