CONTEXT

The discovery that Lectin-Like Transcript 1 (LLT1), also known as C-type lectin domain family 2 member D (CLEC2D), is a ligand for the CD161 receptor, also known as NKRP1A, has led to explore several approches for modulating the activities of cells of the immune system in the purpose of disease treatment. The inventors propose a new approch based on the use of monoclonal antibodies (Mab).
Biological therapeutics are now available for the treatment of certain autoimmune and chronic inflammatory diseases and/or cancer. But there is still a need for alternative biological medicaments which specifically target pathological tissue, which do not affect healthy tissue, which result in less severe side effects, which result in fewer side effects, which may be used long-term, which do not result in the formation of inhibitors. The current invention relates to these unmet needs amongst patients with cancer, and in those with autoimmune and chronic inflammatory diseases.

TECHNICAL DESCRIPTION

The present invention relates to the characterization of monoclonal antibodies that are capable of specifically binding to LLT1, that block the interaction between LLT1 and its receptor CD161 and that have depleting properties in vitro and in vivo. The present invention also relates to polynucleotides encoding such antibodies and cells expressing such antibodies. These Mab have utility in the diagnosis and treatment of cancer and autoimmune/chronic inflammatory diseases, in which LLT1- and CD161- expressing cells play a role in disease pathogenesis.

BENEFITS

The antibodies described in this invention have the potential to modulate immune responses through blocking of the interaction between LLT1 and CD161. The antibodies may be used to stimulate NK cell-mediated anti-tumoral activity or to decrease T cell activation. The antibodies have depleting properties in vitro and in vivo, facilitating the removal of LLT1-expressing cells by antibody-dependent cell-mediated cytotoxicity (ADCC). The antibodies may also be used for diagnosis.

INDUSTRIAL APPLICATIONS

This invention could be used for the treatment of immune–based diseases, mainly cancer and inflammatory/autoimmune disorders, involving LLT1- and CD161- expressing cells in their pathogenesis.

This invention could be useful for the diagnosis of cancer and more specifically B cell non-Hodgkin lymphomas.

DEVELOPMENT STAGE

The inventors have developed murine and chimeric human antibody molecules that specifically bind to LLT1.
They have demonstrated using in vitro assays that the antibodies block the interaction between LLT1 and CD161, thereby stimulating the cytokine production and the cytotoxicity of NK cells and inhibiting the proliferation and the cytokine production of T cells.
They have demonstrated using in vitro assays that the antibodies facilitate the removal of LLT1-expressing cells by antibody-dependent cell-mediated cytotoxicity (ADCC). Preliminary pre-clinical tests in mice xenografted with human B cell lymphomas show in vivo efficacy alone and in combination with rituximab (anti-CD20).

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