Regulatory T cell mediator proteins and uses thereof
The present invention relates to novel regulatory T cell proteins. One protein, designated PD-L3, resembles members of the PD-L1 family, and co-stimulates αCD3 proliferation of T cells in vitro. A second, TNF-like, protein has also been identified as being upregulated upon αCD3/αGITR stimulation. This protein has been designated T reg -sTNF. Proteins, antibodies, activated T cells and methods for using the same are disclosed. In particular methods of using these proteins and compounds, preferably antibodies, which bind or modulate (agonize or antagonize) the activity of these proteins, as immune modulators and for the treatment of cancer, autoimmune disease, allergy, infection and inflammatory conditions, e.g. multiple sclerosis is disclosed.
1. An anti-PD-L3 antibody containing a human constant domain or a human or humanized antibody fragment that binds human PD-L3 which potentially is suitable for use as a human therapeutic or immune modulatory agent that exhibits one or both of the following properties:
(i) inhibits (1) PD-L3 mediated suppression of T cell activation or differentiation; or
(ii) suppresses PD-L3 mediated inhibition of CD4+ or CD8+ T cell proliferation.
2. The antibody or antibody fragment of claim 1 , which is monoclonal.
3. The antibody or antibody fragment of claim 1 , which is human, humanized, or chimeric.
4. The antibody or antibody fragment of claim 1 , which is produced by phage display.
5. The antibody or antibody fragment of claim 1 , which is selected from a Fab fragment, a monovalent antibody fragment consisting of the VL, VH, CL and CH1 domains; a F(ab′)2 fragment, a bivalent fragment comprising two Fab fragments linked by a disulfide bridge at the hinge region; a Fd fragment consisting of the VH and CH1 domains; a Fv fragment consisting of the VL and VH domains of a single arm of an antibody; (v) a dAb fragment which consists of a VH domain; a scFv and a diabody.
6. A pharmaceutical composition comprising an anti-PD-L1 antibody according to claim 1 .
7. The antibody or antibody fragment of claim 1 , that (i) inhibits (1) PD-L3 mediated suppression of T cell activation or differentiation.
8. The antibody or antibody fragment of claim 1 , that (ii) suppresses PD-L3 mediated inhibition of CD4+ or CD8+ T cell proliferation.