Compositions and methods for treatment and detection of cancers

Abstract

Pharmaceutical composition comprising antibodies or antigen binding fragments thereof that bind to globo H, SSEA3, and SSEA-4 are disclosed herein, as well as methods of use thereof. Methods of use include, without limitation, cancer therapies and diagnostics. The antibodies of the disclosure can bind to certain cancer cell surfaces. Exemplary targets of the antibodies disclosed herein can include carcinomas, such as those in brain, skin, bone, lungs, breast, esophagus, stomach, liver, bile duct, pancreas, colon, kidney, cervical, ovarian, and/or prostate cancer.

1 . An isolated humanized monoclonal glycoantibody or antigen-binding fragment thereof that specifically binds to Neu5Acα2→3Galβ1→3GalNAcβ1→3Galα1→4Galβ1→4Glcβ1. 
     
     
         2 . (canceled) 
     
     
         3 . The isolated glycoantibody or antigen-binding fragment thereof of  claim 1 , wherein the antibody is an IgG or IgM. 
     
     
         4 . (canceled) 
     
     
         5 . (canceled) 
     
     
         6 . (canceled) 
     
     
         7 . (canceled) 
     
     
         8 . The isolated antibody or antigen-binding fragment thereof of  claim 1 , wherein the antigen binding fragment is a Fab fragment, a F(ab′)2 fragment, or a single-chain Fv fragment. 
     
     
         9 . The isolated antibody or antigen-binding fragment thereof of  claim 1 , wherein the antibody comprised VH having SEQ ID NO: 147 or SEQ ID No:137 and VL having SEQ ID No: 148 or SEQ ID No:138. 
     
     
         10 . The isolated antibody, or antigen-binding fragment thereof of  claim 1 , comprising wherein the antibody, or antigen-binding fragment thereof comprises an H-CDR1, H-CDR2, and H-CDR3 selected from (i)-(iii):
 (i) H-CDR1 selected from SEQ ID NO:152 (GFSLTSYG);   (ii) H-CDR2 selected from SEQ ID NO: 153 (IWGEGST);   (iii) H-CDR3 selected from SEQ ID NO:154 (AMTGTAY), respectively;   and wherein the antibody, or antigen-binding fragment thereof comprises an L-CDR1, L-CDR2 and L-CDR3 selected from (iv)-(vi):   (iv) L-CDR1 selected from SEQ ID NO: 149 (SSVSY);   (v) L-CDR2 selected from SEQ ID NO:150 (DTS); and   (vi) L-CDR3 selected from SEQ ID NO: 151(HQWSSSPHT), respectively.   
     
     
         11 . The isolated antibody or antigen-binding fragment thereof of  claim 9  wherein the antibody or the antigen binding fragment thereof comprises an H-FR1, H-FR2, H-FR3, and HFR4 selected from (i)-(iv):
 (i) H-FR1 selected from SEQ ID NO:159 (QVQLKESGPGLVAPSQSLSITCTVS); 
 (ii) H-FR2 selected from SEQ ID NO:160 (VSWIRQPPGKGLEWIGV); 
 (iii) H-FR3 selected from SEQ ID NO:161 (NYHSVLISRLTISKDNSKSQVFLKLNSLQTDDTATYYC); 
 (iv) H-FR4 selected from SEQ ID NO:162 (WGQGTLVTVSS); respectively; 
 and wherein the antibody, or antigen-binding fragment thereof comprises an L-FR1, L-FR2, L-FR3 and L-FR4 selected from (v)-(viii): 
 (v) L-FR1 selected from SEQ ID NO: 155 (QIVLTQSPAIMSASPGEKVTMTCSAS); 
 (vi) L-FR2 selected from SEQ ID NO:156 (MHWYQQKSGTSPKRWIY); 
 (vii) L-FR3 selected from SEQ ID NO: 157 (KLSSGVPGRFSGSGSGTSYSLTISRLEAEDAATYYC); 
 (viii) L-FR4 selected from SEQ ID NO: 158 (FGGGTKVEIKR); respectively. 
 
     
     
         12 . A method of treating cancer in a subject in need thereof, wherein the method comprises administering to the subject an effective amount of the isolated antibody of  claim 1  and a pharmaceutically acceptable carrier or a combination thereof. 
     
     
         13 . The method of  claim 12 , wherein the cancer is selected from the group consisting of brain cancer, lung cancer, breast cancer, oral cancer, esophageal cancer, stomach cancer, liver cancer, bile duct cancer, pancreatic cancer, colon cancer, kidney cancer, cervical cancer, ovarian cancer and prostate cancer. 
     
     
         14 . A method for detecting cancer in a subject, comprising:
 (a) applying one or more monoclonal antibodies that detect expression of a panel of markers consisting of GM3, GM2, GM1, GD1, GD1a, GD3, GD2, GT1b, A2B5, LeX, sLeX, LeY, SSEA-3, SSEA-4, sialyl SSEA-4, Globo H, Gb4, TF, Tn, sTn, CD44, CD24, CD45, CD90, CD133/1 and CD133/2 to a cell or tissue sample obtained from the subject;   (b) assaying the binding of the one or more monoclonal antibodies to the cell or the tissue sample; and   (c) comparing the binding with a normal control to determine the presence of the cancer in the subject.   
     
     
         15 . A pharmaceutical composition comprising the antibody or antigen binding fragment thereof according to  claim 1 . 
     
     
         16 . A method of treating cancer in a subject in need thereof, wherein the method comprises administering to the subject a therapeutically effective amount of the immunogenic pharmaceutical composition of  claim 15 . 
     
     
         17 . The method of  claim 16 , wherein a cell of the cancer expresses at least one of Globo H, SSEA3 and/or SSEA4 antigen on the surface of the cell. 
     
     
         18 . The method of  claim 17 , wherein a cell of the cancer expresses SSEA4 antigen on the surface of the cell. 
     
     
         19 . The method of  claim 17 , wherein a cell of the cancer expresses Globo H, SSEA3 and SSEA4 antigen simultaneously on the surface of the cell. 
     
     
         20 . The method of  claim 17 , wherein the cancer is selected from the group consisting of brain cancer, lung cancer, breast cancer, oral cancer, esophageal cancer, stomach cancer, liver cancer, bile duct cancer, pancreatic cancer, colon cancer, kidney cancer, bone cancer (osteosarcoma), skin cancer, cervical cancer, ovarian cancer, and prostate cancer. 
     
     
         21 . The isolated antibody or an antigen binding fragment thereof of  claim 1 , wherein the antibody comprises a N-glycan attached to the Asn-297 of the Fc region wherein the N-glycan consists of the structure of Sia 2 (α2-6)Gal 2 GlcNAc 2 Man 3 GlNAc 2 . 
     
     
         22 . An isolated antibody or an antigen binding fragment thereof, wherein the antibody comprises a N-glycan attached to the Asn-297 of the Fc region of said antibody wherein the N-glycan consists of the structure of Sia 2 (α2-6)Gal 2 GlcNAc 2 Man 3 GlcNAc 2  and wherein the antibody specifically binds to at least one antigen associated with cancers selected from the group consisting of Globo-H, SSEA-3, and SSEA-4. 
     
     
         23 . The isolated antibody of  claim 21  or an antigen binding fragment thereof, wherein the antibody is an anti-SSEA4 specific glycoantibody. 
     
     
         24 . The isolated antibody of  claim 23  or an antigen binding fragment thereof, wherein the antibody is an anti-SSEA4 specific glycoantibody with cross reactivity to Globo-H and/or SSEA3. 
     
     
         25 . (canceled)