Adenocarcinoma specific antibody SAM-6, and uses thereof
The present invention features a polypeptide, such as an antibody produced by the hybridoma SAM-6 and its use in the treatment and diagnosis of neoplasms.
1. A method of treating a proliferative disorder in a mammal, said method comprising the step of administering to the mammal a purified antibody or binding fragment thereof comprising a heavy chain variable region sequence, wherein the heavy chain variable region sequence comprises CDR1, CDR2 and CDR3 shown in SEQ ID NO:3 and is either
(i) at least 90% identical to the amino acid sequence shown in SEQ ID NO:3, or
(ii) encoded by a nucleotide sequence which is at least 90% identical to the nucleotide sequence shown in SEQ ID NO:4.
2. The method of claim 1 , wherein the mammal is a human.
3. The method of claim 1 , wherein the proliferative disorder is an adenocarcinoma of the lung, a squamous cell lung carcinoma, an intestinal type gastric carcinoma, a diffuse type gastric carcinoma, an adenocarcinoma of the colon, an adenocarcinoma of the prostate, a squamous cell carcinoma of the esophagus, an adenocarcinoma of the esophagus, a lobular carcinoma of the breast, a ductal carcinoma of the breast, an adenocarcinoma of the pancreas, an adenocarcinoma of the ovary, or an adenocarcinoma of the uterus.
4. The method of claim 1 , wherein the antibody or binding fragment is conjugated to a detectable agent selected from the group consisting of a radionuclide, a fluorescent marker, an enzyme, a cytotoxin, a cytokine, and a growth inhibitor.
5. The method of claim 4 , wherein the detectable agent is capable of inhibiting cell proliferation.
6. The method of claim 1 , wherein the antibody or binding fragment binds to:
(i) low density lipoproteins (LDL), and/or
(ii) oxidised low density lipoproteins (oxLDL), and/or
(iii) very low density lipoproteins (VLDL).
7. The method of claim 1 , wherein the antibody or binding fragment binds to:
(i) apolipoprotein B comprising low density lipoproteins (LDL), and/or
(ii) apolipoprotein B comprising oxidised low density lipoproteins (oxLDL).
8. The method of claim 1 , wherein the antibody or binding fragment induces the intracellular accumulation of lipids in a cell to which it binds.
9. method of claim 1 , wherein the antibody or binding fragment induces apoptosis of a cell to which it binds.
10. The method of claim 1 , wherein the antibody or binding fragment comprises a light chain variable region sequence, wherein the light chain variable region sequence:
(i) comprises a CDR sequence of the amino acid sequence shown in SEQ ID NO:1, or
(ii) is at least 80% identical to the amino acid sequence shown in SEQ ID NO:1, or
(iii) comprises a CDR sequence encoded by the nucleotide sequence shown in SEQ ID NO:2, or
(iv) is encoded by a nucleotide sequence which is at least 80% identical to the nucleotide sequence shown in SEQ ID NO:2.
11. The method of claim 10 , wherein the CDR sequence comprises the amino acid sequence:
(i) Ser-Gly-Asp-Lys-Leu-Gly-Asp-Lys-Tyr-Ala-Cys, or
(ii) Gln-Asp-Ser-Lys-Arg-Pro-Ser, or
(iii) Gln-Ala-Trp-Asp-Ser-Ser-Ile-Val-Val.
12. The method of claim 10 , wherein the CDR sequence is encoded by a nucleic acid sequence which encodes a CDR sequence of the amino acid sequence shown in SEQ ID NO:1.
13. The method of claim 10 , wherein the antibody or binding fragment comprises a light chain variable region sequence which comprises the three (3) CDR sequences of the amino acid sequence shown in SEQ ID NO:1.
14. The method of claim 10 , wherein the antibody or binding fragment comprises a light chain variable region sequence which comprises the three (3) CDR sequences encoded by the nucleotide sequence shown in SEQ ID NO:2.
15. The method of claim 1 , wherein the antibody is a monoclonal antibody.
16. The method of claim 15 , wherein the monoclonal antibody is a human monoclonal antibody.