The invention provides human monoclonal antibodies or fragments thereof, that specifically bind to CXCR4. Disclosed are methods of use of such antibodies for the treatment and/or prevention of a CXCR4 disease or disorder such as cancer and X4-tropic HIV-1 infection Also provided are methods of use of such antibodies and antibody fragments for the treatment or prevention of cancer metastasis. The invention provides methods of mobilizing CD34+stem cells from the bone marrow and methods of blocking chemotaxis of CXCR4-expressing cells in response to SDF-1. Also provided are methods of use of the antibodies and fragments thereof for the prevention or treatment of graft-versus-host disease. Finally, the invention provides methods of inhibiting new tumor blood vessel formation and/or tumor cell angiogenesis.
