Method, compositions and classification for tumor diagnostics and treatment

• US 20060160157A1
• Filed: 01/19/2006
• Published: 07/20/2006
• Est. Priority Date: 01/19/2005
• Status: Abandoned Application

• Current Assignee: Mathew Mark Zuckerman
• Original Assignee: Mathew Mark Zuckerman
• Inventors: Zuckerman, Mathew Mark
• Application Number:
  US11/334,845
• Publication Number:
  US 20060160157A1
• Time in Patent Office: Days
• US Class Current: 435/7.230
• CPC Class Codes: A61K 51/0476 complexes from monodendate ligands, e.g. sestamibi
• CPC Class Codes: C07K 14/475 Growth factors; Growth regulators
• CPC Class Codes: C07K 14/52 Cytokines; Lymphokines; Interferons
• CPC Class Codes: C07K 14/71 for growth factors; for growth regulators
• CPC Class Codes: C07K 14/715 for cytokines; for lymphokines; for interferons
• CPC Class Codes: G01N 2333/475 Assays involving growth factors
• CPC Class Codes: G01N 2333/485 Epidermal growth factor [EGF] (urogastrone)
• CPC Class Codes: G01N 2500/00 Screening for compounds of potential therapeutic value
• CPC Class Codes: G01N 33/57488 involving compounds identifable in body fluids

Abstract

The present invention is directed towards classifying tumor biomarkers, particularly membrane receptors, and more particularly the gastrin-releasing peptide (GPR) receptors, identified in patient samples, then linking therapeutic agents (chemical, radiological, or biological) to patient-specific ligands that bind to such receptors, clinicians can produce diagnostic and treatment compositions and implement treatment regimens which, by using the classified and identified biomarkers, and due to their improved accuracy, increase success and decrease undesired side effects from such treatments.

Claims

1. A process for the production of a recombinant patient specific tumor receptor ligand, useful in cancer diagnostic and therapeutic applications comprising:

identifying a receptor type present on a cancer cell obtained from a host;

identifying a ligand to that type receptor which ligand is indigenous to said host and which has an ability to bind to said receptor;

providing a plurality of tumor receptor specific ligands associated with said host indigenous ligand, wherein said tumor receptor specific ligands exhibit varying degrees of specificity and/or affinity for aberrantly expressed species of said receptor present on said cancer cell;

deriving a subset of patient specific tumor receptor ligands from said tumor receptor specific ligands; and

deriving or determining a recombinant patient specific tumor receptor ligand;

wherein said recombinant ligand is characterized as exhibiting the highest relative specificity and/or affinity with respect to said subset of patient specific tumor receptor ligands;

whereby providing a ligand equal to said recombinant patient specific tumor receptor ligand is useful in diagnostic and therapeutic applications associated with cancer.

2. The process of claim 1 wherein said receptor type is selected from the group consisting of Epidermal Growth Factor (EGF), Vascular Endothelial Growth Factor (VEGF), Gastrin Releasing Peptide Receptor (GRP-r), or Neuromedin B.

3. The process of claim 1 wherein said receptor is GRP-R.

4. The process of claim 1 wherein said recombinant patient specific tumor receptor ligand is produced by a method selected from the group consisting of protein sequencing, genetic engineering, or mining of a library containing the endogenous end of bacterial phage PIII and PVI proteins.

5. A recombinant patient specific tumor receptor ligand produced in accordance with the process of claim 1.

6. A recombinant patient specific tumor receptor ligand produced in accordance with the process of claim 4.

7. The recombinant patient specific tumor receptor ligand of claim 5 further including at least one radiologic isotope tag selected from the group consisting of 99-Mo (technetium Tc99m), 90-y, 111-In, 123-I, 186-Re, 32-P, 81m-Kr, 89-Sr, 103-Pd, 117m-Sn, 131-I, 47-Sc, 62-Zn, 64-Cu, 68-Ge, 153-Gd, 166-Ho or 177-Lu.

8. The recombinant patient specific tumor recept6r ligand of claim 5 further including at least one chemotherapeutic agent selected from the group consisting of cyclophosphamide, mechlorethamine, mephalin, chlorambucil, heamethylmelamine, thiotepa, busulfan, carmustine, lomustine, semustine, methotrexate, fluorouracil, floxuridine, cytarabine, 6-mercaptopurine, thioguanine, pentostatin, vincristine, vinblastine, vindesine, etoposide, etoposide orthoquinone, and teniposide, daunorubicin, doxorubicin, mitoxantrone, bisanthrene, actinomycin D, plicamycin, puromycin, and gramicidine D, paclitaxel, colchicine, cytochalasin B, emetine, maytansine, and amsacrine, aminglutethimide, cisplatin, carboplatin, mitomycin, altretamine, cyclophosphamide, lomustine (CCNU), carmustine (BCNU), irinotecan (CPT-11), alemtuzamab, altretamine, anastrozole, L-asparaginase, azacitidine, bevacizumab, bexarotene, bleomycin, bortezomib, busulfan, calusterone, capecitabine, celecoxib, cetuximab, cladribine, clofurabine, cytarabine, dacarbazine, denileukin diftitox, diethlstilbestrol, docetaxel, dromostanolone, epirubicin, erlotinib, estramustine, etoposide, ethinyl estradiol, exemestane, fioxuridine, 5-flourouracil, fludarabine, flutamide, fulvestrant, gefitinib, gemcitabine, goserelin, hydroxyurea, ibritumomab, idarubicin, ifosfamide, imatinib, interferon alpha (2a, 2b), irinotecan, letrozole, leucovorin, leuprolide, levamisole, meclorethamine, megestrol, melphalin, mercaptopurine, methotrexate, methoxsalen, mitomycin C, mitotane, mitoxantrone, nandrolone, nofetumomab, oxaliplatin, paclitaxel, pamidronate, pemetrexed, pegademase, pegasparagase, pentostatin, pipobroman, plicamycin, polifeprosan, porfimer, procarbazine, quinacrine, rituximab, sargramostim, streptozocin, tamoxifen, temozolomide, teniposide, testolactone, thioguanine, thiotepa, topetecan, toremifene, tositumomab, trastuzumab, tretinoin, uracil mustard, valrubicin, vinorelbine, or zoledronate.

9. A process for the production of a recombinant patient specific tumor receptor ligand, useful in cancer diagnostic and therapeutic applications comprising:

providing a serum or tissue sample obtained from a host and suspected of containing cancerous cells;

providing a plurality of species of ligands to plural types of receptors, which ligands species are indigenous to said host, and wherein each of said species is known to bind to a receptor found on a cancer cell;

confirming binding of at least one of said species of host indigenous ligands to a cancer cell;

providing a plurality of tumor receptor specific ligands associated with said bound indigenous ligand, wherein said tumor receptor specific ligands exhibit varying degrees of specificity and/or affinity for aberrantly expressed species of said receptor present on said cancer cell;

deriving a subset of patient specific tumor receptor ligands from said tumor receptor specific ligands; and

deriving or determining a recombinant patient specific tumor receptor ligand;

wherein said recombinant ligand is characterized as exhibiting the highest relative specificity and/or affinity with respect to said subset of patient specific tumor receptor ligands;

whereby providing a ligand equal to said recombinant patient specific tumor receptor ligand is useful in diagnostic and therapeutic applications associated with cancer.

10. The process of claim 9 wherein said receptor type is selected from the group consisting of Epidermal Growth Factor (EGF), Vascular Endothelial Growth Factor (VEGF), Gastrin Releasing Peptide Receptor (GRP-r), or Neuromedin B.

11. The process of claim 9 wherein said receptor is GRP-R.

12. The process of claim 9 wherein said recombinant patient specific tumor receptor ligand is produced by a method selected from the group consisting of protein sequencing, genetic engineering, or mining of a library containing the endogenous end of bacterial phage PIII and PVI proteins.

13. A recombinant patient specific tumor receptor ligand produced in accordance with the process of claim 9.

14. A recombinant patient specific tumor receptor ligand produced in accordance with the process of claim 12.

15. The recombinant patient specific tumor receptor ligand of claim 13 further including at least one radiologic isotope tag selected from the group consisting of 99-Mo (technetium Tc99m), 90-y, 111-In, 123-I, 186-Re, 32-P, 81m-Kr, 89-Sr, 103-Pd, 117m-Sn, 131-I, 47-Sc, 62-Zn, 64-Cu, 68-Ge, 153-Gd, 166-Ho or 177-Lu.

16. The recombinant patient specific tumor receptor ligand of claim 13 further including at least one chemotherapeutic agent selected from the group consisting of cyclophosphamide, mechlorethamine, mephalin, chlorambucil, heamethylmelamine, thiotepa, busulfan, carmustine, lomustine, semustine, methotrexate, fluorouracil, floxuridine, cytarabine, 6-mercaptopurine, thioguanine, pentostatin, vincristine, vinblastine, vindesine, etoposide, etoposide orthoquinone, and teniposide, daunorubicin, doxorubicin, mitoxantrone, bisanthrene, actinomycin D, plicamycin, puromycin, and gramicidine D, paclitaxel, colchicine, cytochalasin B, emetine, maytansine, and amsacrine, aminglutethimide, cisplatin, carboplatin, mitomycin, altretamine, cyclophosphamide, lomustine (CCNU), carmustine (BCNU), irinotecan (CPT-11), alemtuzamab, altretamine, anastrozole, L-asparaginase, azacitidine, bevacizumab, bexarotene, bleomycin, bortezomib, busulfan, calusterone, capecitabine, celecoxib, cetuximab, cladribine, clofurabine, cytarabine, dacarbazine, denileukin diftitox, diethlstilbestrol, docetaxel, dromostanolone, epirubicin, erlotinib, estramustine, etoposide, ethinyl estradiol, exemestane, floxuridine, 5-flourouracil, fludarabine, flutamide, fulvestrant, gefitinib, gemcitabine, goserelin, hydroxyurea, ibritumomab, idarubicin, ifosfamide, imatinib, interferon alpha (2a, 2b), irinotecan, letrozole, leucovorin, leuprolide, levamisole, meclorethamine, megestrol, melphalin, mercaptopurine, methotrexate, methoxsalen, mitomycin C, mitotane, mitoxantrone, nandrolone, nofetumomab, oxaliplatin, paclitaxel, pamidronate, pemetrexed, pegademase, pegasparagase, pentostatin, pipobroman, plicamycin, polifeprosan, porfimer, procarbazine, quinacrine, rituximab, sargramostim, streptozocin, tamoxifen, temozolomide, teniposide, testolactone, thioguanine, thiotepa, topetecan, toremifene, tositumomab, trastuzumab, tretinoin, uracil mustard, valrubicin, vinorelbine, or zoledronate.