Colon and pancreas cancer specific antigens and antibodies

a cancer and specific antigen technology, applied in the field of tumor molecular biology, can solve the problems of affecting the patient's health, affecting the detection and treatment of cancer, and affecting the success of cancer diagnosis and treatment, so as to promote tumor regression and slow the growth of tumors

Inactive Publication Date: 2013-07-25
PRECISION BIOLOGICS INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0043]In one embodiment, the invention provides a composition comprising at least two of the following: (a) an antibody, or a fragment thereof, that binds a NPC-1 epitope; (b) an antibody, or a fragment thereof, that recognizes 16C3 epitope, and (c) an antibody, or a fragment thereof, that recognizes an 31.1 epitope. In one embodiment, the invention provides a method for treating cancer comprising administering an effective amount of a composition comprising at least two of the following: (a) an antibody, or a fragment thereof, that binds a NPC-1 epitope; (b) an antibody, or a fragment thereof, that recognizes 16C3 epitope, and (c) an antibody, or a fragment thereof, that recognizes an 31.1 epitope to a patient in need thereof. In one embodiment, the invention provides a method for slowing the growth of a tumor comprising administering an effective amount of a composition comprising at least two of the following: (a) an antibody, or a fragment thereof, that binds a NPC-1 epitope; (b) an antibody, or a fragment thereof, that recognizes 16C3 epitope, and (c) an antibody, or a fragment thereof, that recognizes an 31.1 epitope to a patient in need thereof. The present invention also provides a method for promoting tumor regression in a subject comprising administering an effective amount of a composition comprising at least two of the following: (a) an antibody, or a fragment thereof, that binds a NPC-1 epitope; (b) an antibody, or a fragment thereof, that recognizes 16C3 epitope, and (c) an antibody, or a fragment thereof, that recognizes an 31.1 epitope to a patient in need thereof. The present invention further provides a method for detecting a tumor-associated NPC-1 epitope comprising (a) contacting a test sample with a composition comprising at least two of the following: (i) an antibody, or a fragment thereof, that binds a NPC-1 ep

Problems solved by technology

In later stages of cancer, the tumor cells proliferate at an unusually high rate resulting in uncontrolled growth that threatens the health of the patient known as malignant tumors (or in situ cancer).
National Cancer Institute (2010) “What You Need to Know about Cancer of the Pancreas.” While there have been many advancements in cancer detection and therapy over the last 2 decades, nonetheless the

Method used

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  • Colon and pancreas cancer specific antigens and antibodies
  • Colon and pancreas cancer specific antigens and antibodies
  • Colon and pancreas cancer specific antigens and antibodies

Examples

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example 1

Identification of the NPC-1 Antigen

[0360]The NPC-1 antibody was generated in mice immunized with the so-called “Hollinshead colon cancer vaccine”. Hollinshead, et al. (1985) Cancer 56: 480-489. The NPC-1 antibody and the chimeric form, NPC-1C, are described in U.S. Pat. Nos. 7,314,622 and 7,763,720. Several protein purifications were prepared using both mouse NPC-1 and recombinant, chimeric NPC-1C antibodies. Tumor cell lines including LS174T and HT-29 (human colorectal tumor), CFPAC-1 (human pancreatic tumor), colon cancer patient tumor specimen, and the Hollinshead colon cancer vaccines served as tumor antigen sources for protein extracts. The NPC-1 antigen is secreted into the medium of the human tumor cell lines, and the antigen was purified from tumor cell supernatant of cells grown in the absence of serum for 5 to 7 days. NPC-1 antibody was coupled to resins for the antigen purification, including magnetic beads, for simple adsorption, washing, and elution from the beads. Prot...

example 2

NPC-1 Antigen Knockdown

[0365]A small inhibitory RNA (siRNA) target sequence designed against a region of MUC5AC was used in cells known to express the NPC-1 antigen. Several siRNA oligonucleotides were designed based upon MUC5AC sequences. The sequences of the human MUC5AC siRNA oligonucleotides are shown in Table 7:

TABLE 7Sequence of MUC5AC siRNA oligonucleotidesOligonucleotideStrandSequencesiRNA ID #: s9074SenseAGAUGUGCCUCAACUACGAtt (SEQ ID NO: 120)Anti-SenseUCGUAGUUGAGGCACAUCUtg (SEQ ID NO: 121)siRNA ID #: s9075SenseGCUCUGGAACGUGAGCAUAtt (SEQ ID NO: 122)Anti-SenseUAUGCUCACGUUCCAGAGCcg (SEQ ID NO: 123)siRNA ID #: s9076SenseGCGUGCUCGUCGACAACUAtt (SEQ ID NO: 124)Anti-SenseUAGUUGUCGACGAGCACGCgg (SEQ ID NO: 125)

[0366]The siRNAs were transfected into LS174 and CFPAC-1 tumor cells, as well as A549 cells. A549 is a human lung adenocarcinoma cell line that expresses MUC5AC (as shown by PCR and detection using commercially available antibodies against MUC5AC), but not NPC-1 antigen. The MU...

example 3

NPC-1 Epitope Mapping

[0368]The data by western blots of trypsin-digested MUC5AC indicated that there may be several NPC-1 antibody binding sites on each molecule of MUC5AC, suggesting that a binding region might be present in each of the tandem repeat units located in the central region of the molecule. Therefore, a recombinant expression plasmid was designed and constructed that encoded residues upstream of tandem repeat units and two tandem repeat units (“MUC5AC-long” SEQ ID NO: 3). The MUC5AC long peptide corresponds to amino acid residues 2636 to 2942 of the MUC5AC protein (SEQ ID NO: 1). A second expression plasmid was designed and constructed that encoded primarily a short domain which connects to the central repetitive region and only a portion of the tandem repeat residues (“MUC5AC-short” SEQ ID NO: 5). The MUC5AC short peptide corresponds to amino acid residues 2636 to 2763 of the MUC5AC protein (SEQ ID NO: 1 and FIG. 1). These smaller fragments of the large MUC5AC molecule...

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Abstract

This invention relates to NPC-1 antigen on the MUC5AC protein and 16C3 antigen on CEACAM5 and CEACAM6 proteins, and 31.1 epitope on the A33 protein are differentially expressed in cancers including, lung cancer, ovarian cancer, pancreas cancer, breast cancer, and colon cancer, and diagnostic and therapeutic usages. Further, NPC-1, 16C3, and/or 31.1 epitope specific antibodies and diagnostic and therapeutic methods of use.

Description

CROSS-REFERENCE TO RELATED PATENT APPLICATIONS[0001]This International Patent Application claims priority to U.S. Provisional Patent Application No. 61 / 357,165, filed Jun. 22, 2010; U.S. Provisional Patent Application No. 61 / 359,440, filed Jun. 29, 2010; U.S. Provisional Patent Application No. 61 / 385,587, filed Sep. 23, 2010; U.S. Provisional Patent Application No. 61 / 407,112, filed Oct. 27, 2010; U.S. Provisional Patent Application No. 61 / 435,163, filed Jan. 21, 2011; U.S. Provisional Patent Application No. 61 / 435,176, filed Jan. 21, 2011; and U.S. Provisional Patent Application No. 61 / 467,896, filed Mar. 25, 2011, the disclosures of each of which are herein incorporated by reference.BACKGROUND OF THE INVENTIONMolecular Biology of Cancer[0002]Cancer is caused by a malfunction in the growth control systems of a cell. Cells control their growth via combination of proliferation inhibition by tumor suppressor genes (e.g., Retinoblastoma protein (pRb), p53) and proliferation activation ...

Claims

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Application Information

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IPC IPC(8): C07K14/705C07K7/08
CPCA61K51/1063C07K14/705C07K7/08C07K16/2803A61P35/00A61P37/04
Inventor DU, XIULIANLUKA, JANOSSTAFFORD, LEWIS JOESEMENUK, MARKWANG, XUE-PINGKANTOR, JUDITHBRISTOL, ANDREW J.
Owner PRECISION BIOLOGICS INC
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