Human monoclonal antibodies to immunoglobulin superfamily receptor translocation- associated-3, -4 and -5 molecules as potential therapeutic agents for B-cell malignancies

Abstract

B-cell malignancies, which include various forms of leukaemias and lymphomas as well as multiple myelomas, arise from neoplastic transformation of B-cells at distinct stages of differentiation and result in significant morbidity and mortality. The introduction of therapeutic mAbs against B-cell surface antigens has brought major improvements in disease outcome for several forms of B-cell malignancies. However, a substantial proportion of patients still succumb to these diseases and there is a crucial need for additional reagents directed at novel B-cell surface molecules. Ig superfamily receptor translocation-associated (IRTA) molecules may provide such new targets. IRTA molecules (also called Fc receptor homologues) are cell surface glycoproteins that contain 3 – 9 Ig domains in their extracellular regions and consensus immunoreceptor tyrosine-based activation and/or inhibitory motifs in their cytoplasmic tails. This family of molecules comprises six members, five of which (IRTA-1, -2, -3, -4 and -5) are preferentially expressed during B-cell differentiation. Preliminary evidence indicates that B-cell-associated IRTA molecules are also differentially expressed in various B-cell malignancies. As an approach to exploit the possible therapeutic value of IRTA molecules, Medarex has generated and characterised fully human mAbs with specificity and high affinity for IRTA-3, -4 or -5. These mAbs are claimed to be potentially useful for the treatment of B-cell malignancies, but this remains to be further investigated.

Keywords::

• B-cell differentiation
• B-cell malignancies
• chronic lymphocytic leukaemia
• Fc receptor homologue
• immunoglobulin superfamily receptor translocation-associated
• IRTA-2
• IRTA-4
• IRTA-5
• immunotherapy
• non-Hodgkin’s lymphoma

Patent Details

• Title IRTA-5 antibodies and their uses.

• Assignee Medrarex, Inc.

• Inventors Graziano R, Cardarelli JM, Kempe T, Cutter B, Srinivasan M.

• Priority date 29/03/05.

• Filing date 29/03/05.

• Publication date 29/10/05.

• Publication no WO2005097185.

• Title IRTA-4 antibodies and their uses.

• Assignee Medarex, Inc.

• Inventors Srinivasan M, Cardarelli JM, Huang H.

• Priority date 29/09/04.

• Filing date 19/09/05.

• Publication date 13/04/06.

• Publication no WO2006039135.

• Title IRTA-2 antibodies and their uses.

• Assignee Medarex, Inc.

• Inventors Grazino R, King DJ, Srinivasan M, Cardarelli JM, Huang H.

• Priority date 12/01/06.

• Filing date 12/01/06.

• Publication date 20/07/06.

• Publication no WO2006076691.