ANTI-NME ANTIBODY AND METHOD OF TREATING CANCER OR CANCER METASTASIS
The present application discloses anti-NME antibodies and their use in treating or preventing diseases.
1 . An NME7 specific antibody or fragment thereof that binds to the NME7 B3 peptide of SEQ ID NO:145 or SEQ ID NO:169.
2 . The antibody of claim 1 , which is a monoclonal antibody.
3 . The antibody of claim 1 , which is bivalent, monovalent, an Fab, or a single chain variable fragment antibody (scFv).
4 . The antibody of claim 1 , which is linked to an antibody drug conjugate.
5 . The antibody of claim 1 , wherein the drug is linked to a toxin or pro-toxin.
6 . An isolated nucleic acid encoding the monoclonal antibody according to claim 2 .
7 . An isolated hybridoma expressing the monoclonal antibody according to claim 2 .
8 . The antibody of claim 1 , which specifically binds to NME7 AB or NME7-X1, but not to NME1.
9 . The antibody of claim 1 that disrupts interaction between NME7 AB and MUC1* extra cellular domain or between NME7-X1 and MUC1* extra cellular domain.
10 . The antibody of claim 1 that disrupts binding between NME7 AB and PSMGFR or between NME7-X1 and PSMGFR.
11 . The antibody of claim 1 that disrupts binding between NME7 AB and N-10 or between NME7-X1 and N-10.
12 . The antibody of claim 1 that does not disrupt interaction between NME7 AB and MUC1* extra cellular domain or between NME7-X1 and MUC1* extra cellular domain, wherein the NME7 AB or NME7-X1 binds to the N-10 peptide (SEQ ID NO:170) but not to a C-10 peptide (SEQ ID NO:171).
13 . The antibody of claim 2 , wherein the antibody is 5A1, 4A3, 4P3 or 5D4.
14 . The antibody of claim 2 , comprising an amino acid sequence in the heavy chain variable region comprising the following:
in the CDR1 region YTFTNYGMN (SEQ ID NO:439);
in the CDR2 region WINTYTGEPTYVDDFKG (SEQ ID NO:440); and
in the CDR3 region LRGIRPGPLAY (SEQ ID NO:441); and
an amino acid sequence in the light chain variable region comprising the following:
in the CDR1 region SASSSVSYMN (SEQ ID NO:444);
in the CDR2 region GISNLAS (SEQ ID NO:445); and
in the CDR3 region QQRSSYPPT (SEQ ID NO:446).
15 . The antibody of claim 2 , comprising an amino acid sequence in the heavy chain variable region comprising the following:
in the CDR1 region NTFTEYTMH (SEQ ID NO:388);
in the CDR2 region GFNPNNGVTNYNQKFKG (SEQ ID NO:389); and
in the CDR3 region RYYHSLYVFYFDY (SEQ ID NO:390); and
an amino acid sequence in the light chain variable region comprising the following:
in the CDR1 region SASQGISNYLN (SEQ ID NO:393);
in the CDR2 region YTSSLHS (SEQ ID NO:394); and
in the CDR3 region QQYSKLPYT (SEQ ID NO:395).
16 . The antibody of claim 2 , comprising an amino acid sequence in the heavy chain variable region comprising the following:
in the CDR1 region NTFTEYTMH (SEQ ID NO:429);
in the CDR2 region GFNPNNGVTNYNQKFKG (SEQ ID NO:430); and
in the CDR3 region RYYHSTYVFYFDS (SEQ ID NO:431); and
an amino acid sequence in the light chain variable region comprising the following:
in the CDR1 region SASQGISNYLN (SEQ ID NO:434);
in the CDR2 region YTSSLHS (SEQ ID NO:435); and
in the CDR3 region QQYSKLPYT (SEQ ID NO:436).
17 . The antibody of claim 2 , comprising an amino acid sequence in the heavy chain variable region comprising the following:
in the CDR1 region NTFTEYTMH (SEQ ID NO:388);
in the CDR2 region GFNPNNGVTNYNQKFKG (SEQ ID NO:389); and
in the CDR3 region RYYHSLYVFYFDY (SEQ ID NO:390); and
an amino acid sequence in the light chain variable region comprising the following:
in the CDR1 region ITSTDIDDDMN (SEQ ID NO:);
in the CDR2 region EGNTLRP (SEQ ID NO:); and
in the CDR3 region LQSDNLPLT (SEQ ID NO:).
18 . The antibody of claim 1 , which is human, humanized or an engineered antibody mimic.
19 . The antibody of claim 1 , which is non-human.
20 . The antibody of claim 19 , which is murine or camelid.
21 . A method of administering to a patient for prevention or treatment of cancer comprising administering to the patient a composition comprising the antibody of claim 1 - claim 17 .
22 . A method for preventing or treating cancer metastasis in a patient, comprising administering to the patient a composition comprising the antibody of claim 1 - claim 17 .
23 . A method for diagnosing cancer or cancer metastasis comprising contacting a patient specimen and normal specimen with the antibody of claim 1 - claim 17 , and comparing the results from both specimen, wherein presence of positive binding to the antibody in the patient specimen indicates the presence of cancer or cancer metastasis in the patient.
24 . The method of claim 23 , wherein the antibody is as set forth in claim 12 .
25 . The method of claim 22 , wherein the antibody is linked to an imaging agent.
26 . The method of claim 22 , wherein the patient specimen is blood, bodily fluid, tissue, circulating cells, in vitro, in vivo, including intra-operative.
27 . A cell that is engineered to express an anti-NME7 AB antibody or fragment thereof.
28 . The cell of claim 27 , wherein the cell is an immune cell.
29 . The cell of claim 27 , wherein the immune cell is T cell or NK cell.
30 . The cell of claim 27 , wherein the cell is a stem or progenitor cell.
31 . The cell of claim 30 , wherein the stem or progenitor cell that is then differentiated to become a T cell.
32 . The cell of claim 27 , which comprises chimeric antigen receptor (CAR) that recognizes tumor associated antigen.
33 . The cell of claim 27 , wherein expression of the anti-NME7 antibody is inducible.
34 . The cell of claim 27 , where nucleic acid encoding an anti-NME7 AB antibody is inserted into the Foxp3 enhancer or promoter.
35 . The cell of claim 27 , wherein an anti-NME7 AB antibody is in an NFAT-inducible system.
36 . The cell of claim 35 , wherein NFATc1 response element, which is inserted upstream of the antibody sequence that is inserted into Foxp3 enhancer or promoter region.
37 . The cell of claim 27 , wherein the anti-NME7 AB antibody or fragment thereof binds to the NME7 B3 peptide, or disrupts binding of NME7 AB or NME7-X1 to the PSMGFR peptide of the MUC1* extra cellular domain.
38 . The immune cell of claim 28 , comprising expresses a CAR that recognizes a tumor associated antigen and an anti-NME7 antibody.
39 . The immune cell of claim 38 , wherein the tumor associated antigen is MUC1*.
40 . An anti-cancer vaccine comprising a composition comprising one or more peptides derived from NME7 AB listed in FIG. 6 - FIG. 9 or a peptide having at least 80%, 85%, 90%, 95%, 97% sequence identity thereof as the immunogenicity eliciting portion.
41 . The anti-cancer vaccine of claim 40 , wherein the peptide is a peptide of SEQ ID NOS:141-145 or a peptide having at least 80%, 85%, 90%, 95%, 97% sequence identity thereof.
42 . The anti-cancer vaccine of claim 41 , wherein the peptide is a peptide of SEQ ID NOS: 145 or a peptide having at least 80%, 85%, 90%, 95%, 97% sequence identity thereof.
43 . A BiTE comprising the antibody of claim 1 - claim 17 .
44 . A method of generating anti-NME7 AB antibodies wherein Cysteine residue in the NME7 B3 peptide is mutated to avoid disulfide bonding.
45 . The method of claim 44 , wherein the Cysteine that is mutated to avoid disulfide bonding is Cysteine 14 of the peptide of SEQ ID NO:169.
46 . A method of generating cells with enhanced metastatic potential comprising culturing the cells with NME7 AB or NME7-X1.
47 . A cell that is engineered to express NME7 AB or NME7-X1.
48 . A transgenic animal that expresses NME7 AB or NME7-X1.
49 . The transgenic animal of claim 48 , wherein the NME7 AB or NME7-X1 is human.
50 . The transgenic animal of claim 49 , wherein expression of NME7 AB or NME7-X1 is inducible.
51 . A bispecific antibody comprising a fragment of the sequence of the antibody of claim 1 - claim 17 .