Humanized anti-CD134 (OX40) antibodies and uses thereof
The invention provides antibodies that specifically bind to human CD134. Anti-human CD134 antibodies specifically bind to the extracellular domain of human CD134, including non-OX40 ligand (OX40L) binding domains on human CD134, which is expressed on e.g. activated human conventional effector CD4 and/or CD8 T lymphocytes (Teffs) and on activated human suppressive regulatory CD4 T lymphocytes (Tregs). Humanized anti-human CD134 antibodies are useful (e.g. to empower Teffs anti-cancer effector function and/or to inhibit Tregs suppressive function) for cancer treatment.
1. An isolated antibody that binds human CD134, comprising a light chain variable region (VL) and a heavy chain variable region (VH), wherein the VL comprises SEQ ID NO:63 and the VH comprises SEQ ID NO:66.
2. The antibody of claim 1 , wherein the antibody is humanized.
3. The antibody of claim 1 , wherein the antibody is an agonist of CD134.
4. The antibody of claim 3 , wherein the antibody is of IgG1, IgG2, IgG3 or IgG4 isotype.
5. The antibody of claim 4 , wherein the antibody comprises a substitution in an Fc region.
6. The antibody of claim 5 , wherein the substitution modulates binding of the antibody to an Fc gamma receptor (FcγR) or to a neonatal Fc receptor (FcRn).
7. A pharmaceutical composition comprising the antibody of claim 1 and a pharmaceutically acceptable carrier.