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. A method of treating cancer by potentiating anti-tumor immunity comprising administering an effective amount of an anti-PD-L3 antibody or antibody fragment that specifically binds to the extracellular region of the human PD-L3 protein having the sequence in SEQ ID NO:4, wherein said anti-PD-L3 antibody or antibody fragment antagonizes the immunosuppressive effect of PD-L3 on immune cells n vivo, and thereby potentiates anti-tumor immunity.
2. The method of claim 1 , wherein the anti-PD-L3 antibody, antibody fragment antagonizes one or more of the following effects of PD-L3 in vivo:
(1) suppression of T cell activation or differentiation;
(2) suppression of CD4+ or CD8+ T cell proliferation, and
(3) suppression of cytokine production by T cells.
3. The method of claim 1 , wherein the cancer is selected from sarcoma, melanoma, lymphoma, leukemia, neuroblastoma, and carcinoma.
4. The method of claim 3 , wherein the cancer is melanoma.
5. The method of claim 1 , wherein the antibody or antibody fragment is a chimeric, human or humanized antibody or fragment thereof.
6. The method of claim 1 , wherein the antibody fragment is selected from a Fab, F(ab′)2, Fv, Fd, and a scFv.
7. The method of claim 1 , wherein the antibody is an IgG1.