Novel Diagnostics and Therapeutics for Various Hematologic Malignancies: Monoclonal Antibodies to Members of Fc receptor-like (FCRL) Proteins
Description of Invention:
Fc receptor-like (FCRL) is a gene family homologous to Fc receptors (alternative names, FcRH, IRTA, IFGP, SPAP). FCRL1-6 genes are located on human chromosome 1, where translocations and other abnormalities are frequently observed in certain B-cell lymphoma and multiple myeloma. Previous studies suggests that the FCRL proteins are differently expressed on various malignant cells from B-linage cells as well as normal B cells in different stage of the differentiation in adaptive immunity. Although the natural ligands are not known, FCRL proteins likely play roles in regulation of immunity. The members of the immunoglobulin superfamily receptor translocation associated (IRTA) genes 1-6 encode proteins homologous to Fc receptors. Previous studies suggest that each IRTA may play a different role in B-cell differentiation and immune responses. FCRL1-6 proteins possess 3-9 extracellular immunoglobulin (Ig) domains, each of which exhibits a substantial homology to the same subtypes of Ig domains (up to 86% identity). Consequently there are some epitopes shared by FCRL1-6 extracellular domains evidenced by the presence of many cross-reactive monoclonal antibodies (MAbs) with FCRL1-6. The invention relates to the development of novel MAbs specific to each member of the FCRL proteins, which show no cross-reactivity with other FCRL members. These antibodies could be used for studies on detailed expression studies of FCRLs in different cancer cells and on potential therapeutic use for FCRL-expressing hematological malignancies.
Applications and Modality:
Novel monoclonal antibodies to FCRL family members can help diagnose and treat B cell malignancies and RA.
The antibodies can be used as research tools to detect cellular expression of FCRLs.
Advantage:
Monoclonal antibody clones are available that are specific to one member of the FCRL family with no cross-reactivity to other members.
Development Status:
The technology is in pre-clinical stage of development.
Patent Status:
DHHS Reference No. E-016-2006/0 --
U.S. Provisional Application No. 60/891,434, filed 23 Feb 2007, entitled "Antibodies That Specifically Bind IRTA and Methods of Use"
PCT Application No. PCT/US2008/054720 filed 22 Feb 2008, entitled "Antibodies That Specifically Bind IRTA and Methods of Use," which published as WO 2008/103905 on 28 Aug 2008
DHHS Reference No. E-287-2004/1 --
PCT Application No. PCT/US2005/034444 filed 22 Sep 2005, entitled "IRTA2 Antibodies and Methods of Use," which published as WO 2006/039238 on 25 Jan 2007
U.S. Patent Application No. 11/664,211 filed 28 Mar 2007, entitled "IRTA2 Antibodies and Methods of Use"
Relevant Publication:
A manuscript directly related to this technology will be available as soon as it is accepted for publication.
T Ise, H Maeda, K Santora, L Xiang, RJ Kreitman, I Pastan, S Nagata. Immunoglobulin superfamily receptor translocation associated 2 protein on lymphoma cell lines and hairy cell leukemia cells detected by novel monoclonal antibodies. Clin Cancer Res. 2005 Jan 1;11(1):87-96. [PubMed abs]
T Ise, RJ Kreitman, I Pastan, S Nagata. Sandwich ELISAs for soluble immunoglobulin superfamily receptor translocation-associated 2 (IRTA2)/FcRH5 (CD307) proteins in human sera. Clin Chem Lab Med. 2006;44(5):594-602. [PubMed abs]
T Ise, S Nagata, RJ Kreitman, WH Wilson, AS Wayne, M Stetler-Stevenson, MR Bishop, DA Scheinberg, L Rassenti, TJ Kipps, RA Kyle, DF Jelinek, I Pastan. Elevation of soluble CD307 (IRTA2/FcRH5) protein in the blood and expression on malignant cells of patients with multiple myeloma, chronic lymphocytic leukemia, and mantle cell lymphoma. Leukemia. 2007 Jan;21(1):169-174. [PubMed abs]
Licensing Status: Available for exclusive and non-exclusive licensing.
Portfolios: Cancer
Cancer -Diagnostics-In Vitro-MAb Based Cancer -Therapeutics-Immunoconjugates-Mab Cancer -Diagnostics Cancer -Therapeutics
For Additional Information Please Contact: David A. Lambertson Ph.D.
NIH Office of Technology Transfer
6011 Executive Blvd, Suite 325
Rockville, MD 20852-3804
Phone: (301)435-4632
Email: lambertsond@mail.nih.gov
Fax: (301) 402-0220
