The technology describes the humanization of a murine anti-carcinoma antibody CC49 which has been shown to react with Tumor Associated Glycoprotein 72 (TAG-72), an antigen which is expressed on human breast, ovarian, colorectal, and other carcinomas.

The invention includes a new method of humanization of a rodent antibody which is based on grafting all the Complementarity Determining Residues (CDRs) of a rodent antibody onto a human antibody framework. Additionally, the method identifies Specificity Determining Residues (SDRs), the amino acid residues in the hypervariable regions of an antibody that are most critical for antigen binding activity and of rendering any antibody minimally immunogenic in humans by transferring the SDRs of the antibody to a human antibody framework. The resulting humanized antibodies, including CDR variants thereof (including a CH2 deleted version), are also embodied in the invention, as are methods of using the antibodies for therapeutic and diagnostic purposes.

Furthermore, these antibodies are suitable for radiolabeling for the application in radioimmunotherapy (RIT) based treatment of several cancers. Phase I results of radioimmunotherapy for ovarian cancer using ⁹⁰Yttrium-CC49 murine monoclonal antibodies have shown promising results and confirms feasibility of the use of these antibodies for RIT. Promising pharmacokinetic data for the radiolabeled humanized antibodies in colon carcinoma xenograft models were recently published.

Applications and Modality:

• A humanized anti-cancer CC49 monoclonal antibody has been developed.
• New methods of humanization of rodent antibodies have been identified.
• The antibody(s) has been shown to react with Tumor Associated Glycoprotein 72 (TAG-72), an antigen which is expressed on human breast, ovarian, colorectal, and other carcinomas.
• These antibodies are suitable for radiolabeling for the application in radioimmunotherapy (RIT) based treatment of several cancers.
• These antibodies can be useful in diagnosis and treatment of several cancers.

Development Status:
The technology is currently in the pre-clinical stage of development. Phase I results of radioimmunotherapy for ovarian cancer using ⁹⁰Yttrium-CC49 murine monoclonal antibodies have shown promising results and confirms feasibility of the use of these antibodies for radioimmunotherapy (RIT).

Publications:

1. RD Alvarez et al. A Phase I study of combined modality ⁹⁰Yttrium-CC49 intraperitoneal radioimmunotherapy for ovarian cancer. Clin Cancer Res. 2002 Sep;8(9):2806-2811. [PubMed abs]
2. A Forero et al. A novel monoclonal antibody design for radioimmunotherapy. Cancer Biother Radiopharm. 2003 Oct;18(5):751-759. [PubMed abs]
3. PC Chinn et al. Pharmacokinetics and tumor localization of ¹¹¹in-labeled HuCC49deltaCH2 in BALB/c mice and athymic murine colon carcinoma xenograft. Cancer Biother Radiopharm. 2006 Apr;21(2):106-116. [PubMed abs]

Preclinical

HHS Reference No. E-259-1998/2 --

• U.S. Patent No. 6,818,749 issued 16 Nov 2004
• U.S. Patent No. 7,256,004 issued 14 Aug 2007
• Issued and pending foreign counterparts

HHS Reference No. D-003-1992/0 --

• European Patent No. 00365997 issued 14 Sep 1994 and its counterpart in Japan

HHS Reference No. D-003-1992/2 --

• U.S. Patent No. 5,472,693 issued 05 Dec 1995
• U.S. Patent No. 5,993,813 issued 30 Nov 1999
• U.S. Patent No. 6,641,999 issued 04 Nov 2003

HHS Reference No. D-003-1992/3 --

• U.S. Patent No. 6,051,225 issued 18 Apr 2000

HHS Reference No. D-004-1992/0 --

• European Patent No. 628078 issued 08 Dec 1999 and its counterparts in Japan, Canada, and Australia

HHS Reference No. D-004-1992/1 --

• U.S. Patent No. 5,877,291 issued 02 Mar 1999
• U.S. Patent No. 5,892,020 issued 06 Apr 1999 and its foreign counterparts

HHS Reference No. D-001-1996/0 --

• Taiwanese Patent No. 173667 issued 10 Jul 2003

HHS Reference No. D-001-1996/1 --

• U.S. Patent No. 6,737,060 issued 18 May 2004
• U.S. Patent No. 6,737,061 issued 18 May 2004
• U.S. Patent No. 6,753,152 issued 22 Jun 2004
• U.S. Patent No. 6,752,990 issued 22 Jun 2004

HHS Reference No. D-001-2006/0 --

• U.S. Patent No. 6,329,507 issued 11 Dec 2001
• U.S. Patent No. 6,071,515 issued 06 Jun 2000

Inventors:
Syed V. Kashmiri (NCI), Eduardo A. Padlan (NIDDK), Jeffrey Schlom (NCI)

Licensing Status:
Available for licensing.

Collaborative Research Opportunity:
The National Cancer Institute's Laboratory of Tumor Immunology and Biology is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize anti-carcinoma antibodies. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.