Antibodies to the Human Prolactin Receptor

Abstract

This invention provides antibodies to the prolactin receptor, particularly the human prolactin receptor. Preferred antibodies are capable of blocking prolactin binding to the prolactin receptor, inhibiting signaling through the prolactin receptor, and/or inhibiting proliferation of cancer cells induced by prolactin. Also provided are nucleic acids encoding the antibodies, vectors and host cells comprising the nucleic acids, and uses of the antibodies and nucleic acids.

1 . A hybridoma deposited at the American Type Culture Collection (ATCC) as PTA-6477, PTA-6478, PTA-6479, PTA-6480, or PTA-6481. 
     
     
         2 . An isolated antibody produced by the hybridoma of  claim 1 . 
     
     
         3 . An isolated antibody recognizing the same epitope as the antibody of  claim 2 . 
     
     
         4 . The antibody of  claim 3  that is a humanized antibody, chimeric antibody, single chain antibody, Fab fragment, Fab′ fragment, F(ab′)2 fragment, or Fv fragment. 
     
     
         5 . The antibody of  claim 3  comprising a detectable label. 
     
     
         6 . A pharmaceutical composition comprising the antibody of  claim 2 . 
     
     
         7 . The pharmaceutical composition of  claim 6  further comprising a chemotherapeutic agent. 
     
     
         8 . The pharmaceutical composition of  claim 6  further comprising an additional antibody. 
     
     
         9 . The pharmaceutical composition of  claim 8  wherein the additional antibody recognizes the human prolactin receptor. 
     
     
         10 . An isolated nucleic acid comprising a sequence encoding the antibody of  claim 2 . 
     
     
         11 . A pharmaceutical composition comprising the nucleic acid of  claim 10 . 
     
     
         12 . A vector comprising the nucleic acid of  claim 10 . 
     
     
         13 . A host cell comprising the vector of  claim 12 . 
     
     
         14 . The host cell of  claim 13  that is bacterial or mammalian. 
     
     
         15 . A method of producing an antibody, comprising culturing the host cell of  claim 13  and harvesting the antibody from the culture of the host cell. 
     
     
         16 . The method of  claim 15  wherein the antibody is harvested from the supernatant of the host cell. 
     
     
         17 . A method of inhibiting signaling through a prolactin receptor in a cell, comprising contacting the cell with an effective amount of the antibody of  claim 2 . 
     
     
         18 . The method of  claim 17  wherein the cell is a breast cancer cell. 
     
     
         19 . The method of  claim 17  wherein the cell is a colon cancer cell, prostate cancer cell, uterine cancer cell, leukemia cell or kidney cancer cell. 
     
     
         20 . A method of inhibiting prolactin-induced proliferation of a cell, comprising contacting the cell with the antibody of  claim 2 . 
     
     
         21 . The method of  claim 20  wherein the cell is selected from the group consisting of breast cancer cells, colon cancer cells, prostate cancer cells, uterine cancer cells, leukemia cells, and kidney cancer cells. 
     
     
         22 . A method of treating breast cancer in a mammal, comprising administering an effective amount of the antibody of  claim 2  to the mammal. 
     
     
         23 . The method of  claim 22  further comprising administering an additional antibody to the mammal. 
     
     
         24 . The method of  claim 23  wherein the additional antibody recognizes the human prolactin receptor. 
     
     
         25 . The method of  claim 23  wherein the additional antibody is Herceptin®. 
     
     
         26 . The method of  claim 22  further comprising administering a chemotherapeutic agent to the mammal. 
     
     
         27 . The method of  claim 22  wherein the mammal is human. 
     
     
         28 . An isolated antibody that recognizes a human prolactin receptor but not mouse prolactin receptor, wherein the antibody inhibits signaling through the human prolactin receptor. 
     
     
         29 . The antibody of  claim 28  that inhibits prolactin-induced proliferation of a cell. 
     
     
         30 . The antibody of  claim 29  wherein the cell is a breast cancer cell. 
     
     
         31 . The antibody of  claim 28  that binds to the human prolactin receptor with an affinity of 1 nM or less.