# US 8,465,738 B2 · Use of vascular endothelial growth factor receptor 1+ cells in treating and monitoring cancer and in screening for chemotherapeutics > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 8,465,738 B2 - Document ID: US8465738B2 - Status: Granted - Kind: B2 - Application number: 12/564,683 - Filed: 2009-09-22 - Published: 2010-06-17 - Granted: 2013-06-18 - Earliest claimed: 2004-11-19 - Assignees: Cornell Research Foundation, Inc. - Applicants: David Lyden; Rosandra N. Kaplan; Rebecca D. Riba; Shahin Rafii - Inventors: David Lyden; Rosandra N. Kaplan; Rebecca D. Riba; Shahin Rafii - Web page: https://patentgrep.com/patent/US8465738B2 ## CPC - C07K 16/2842: {against integrin beta1-subunit-containing molecules, e.g. CD29, CD49} - A61P 35/00: Antineoplastic agents - C07K 16/2863: {against receptors for growth factors, growth regulators} - G01N 33/5011: {for testing antineoplastic activity} - G01N 33/5044: {involving specific cell types} - A61K 2039/505: {comprising antibodies} - C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding - G01N 2333/71: for growth factors; for growth regulators - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q) - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) ## Abstract The present invention is directed to a method of inhibiting tumor formation in a cancer patient at a site remote from sites of prior tumor formation and to a method of preventing metastases. These methods involve administering to the cancer patient an inhibitor of vascular endothelial growth factor receptor 1+ bone marrow-derived cells under conditions effective either to inhibit tumor formation in the cancer patient at a site remote from sites of prior tumor formation or to prevent metastases. Candidate compounds useful for such purposes can be screened depending on whether they bind to vascular endothelial growth factor receptor 1+ bone marrow-derived cells. Metastases in a cancer patient can be monitored by evaluating a patient sample for detection and quantification of vascular endothelial growth factor receptor 1+ bone marrow-derived cells and comparing the level of vascular endothelial growth factor receptor 1+ bone marrow-derived cells to prior levels. ## Claims ### Claim 1 A method of inhibiting tumor formation in a cancer patient at a site remote from sites of prior tumor formation, said method comprising: selecting a cancer patient having an increased blood or tissue level of vascular endothelial growth factor receptor 1+ (VEGFR1+) bone marrow derived progenitor cells compared to a prior measured level of VEGFR1+ bone marrow derived progenitor cells in the patient and administering to the selected cancer patient an inhibitor of vascular endothelial growth factor receptor 1+ bone marrow-derived progenitor cells selected from the group consisting of a VEGFR1 inhibitor, a VLA-4 inhibitor, and an MMP-9 inhibitor under conditions effective to inhibit tumor formation in the cancer patient at a site remote from sites of prior tumor formation. ### Claim 2 (depends on 1) The method according to claim 1, wherein said administering is carried out at a time period corresponding to when vascular endothelial growth factor receptor 1+ bone marrow-derived progenitor cell mobilization is stimulated. ### Claim 3 (depends on 2) The method according to claim 2, wherein vascular endothelial growth factor receptor 1+ bone marrow-derived progenitor cell mobilization is stimulated by chemotherapy, stress, surgery, inflammation, irradiation, or growth factors. ### Claim 4 (depends on 3) The method according to claim 3, wherein vascular endothelial growth factor receptor 1+ bone marrow-derived progenitor cell mobilization is stimulated by chemotherapy. ### Claim 5 (depends on 3) The method according to claim 3, wherein vascular endothelial growth factor receptor 1+ bone marrow-derived progenitor cell mobilization is stimulated by stress. ### Claim 6 (depends on 3) The method according to claim 3, wherein vascular endothelial growth factor receptor 1+ bone marrow-derived progenitor cell mobilization is stimulated by surgery. ### Claim 7 (depends on 3) The method according to claim 3, wherein vascular endothelial growth factor receptor 1+ bone marrow-derived progenitor cell mobilization is stimulated by mobilization of inflammatory cells. ### Claim 8 (depends on 3) The method according to claim 3, wherein vascular endothelial growth factor receptor 1+ bone marrow-derived progenitor cell mobilization is stimulated by irradiation. ### Claim 9 (depends on 3) The method according to claim 3, wherein vascular endothelial growth factor receptor 1+ bone marrow-derived progenitor cell mobilization is stimulated by growth factors. ### Claim 10 (depends on 9) The method according to claim 9, wherein the growth factors are selected from the group consisting of granulocyte colony stimulating factors, granulocyte macrophage stimulating factors, and growth hormones that stimulate bone marrow cell growth. ### Claim 11 (depends on 1) The method according to claim 1, wherein the inhibitor of vascular endothelial growth factor receptor 1+ bone marrow-derived progenitor cells binds to vascular endothelial growth factor receptor 1+ bone marrow-derived progenitor cells. ### Claim 12 (depends on 1) The method according to claim 1, wherein the inhibitor of vascular endothelial growth factor receptor 1+ bone marrow-derived progenitor cells prevents or reduces formation of vascular endothelial growth factor receptor 1+ bone marrow-derived progenitor cells. ### Claim 13 (depends on 1) The method according to claim 1, wherein the inhibitor of vascular endothelial growth factor receptor 1+ bone marrow-derived progenitor cells is a vascular endothelial growth factor receptor 1+ bone marrow-derived progenitor cell-specific antibody or antigen-binding portion thereof. ### Claim 14 (depends on 13) The method according to claim 13, wherein a polyclonal antibody is administered. ### Claim 15 (depends on 13) The method according to claim 13, wherein a monoclonal antibody is administered. ### Claim 16 (depends on 13) The method according to claim 13, wherein an antigen-binding portion of an antibody is administered. ### Claim 17 (depends on 1) The method according to claim 1, wherein the inhibitor is an antibody or antigen-binding portion of an antibody capable of binding to VLA-4 (α4β1) integrin. ### Claim 18 (depends on 1) The method according to claim 1, wherein said administering is part of an adjuvant therapy regime. ### Claim 19 A method of preventing metastases in a cancer patient, said method comprising: selecting a cancer patient having an increased blood or tissue level of vascular endothelial growth factor receptor 1+ (VEGFR1+) bone marrow derived progenitor cells compared to a prior measured level of VEGFR1+ bone marrow derived progenitor cells in the patient and administering to the selected cancer patient an inhibitor of vascular endothelial growth factor receptor 1+ bone marrow-derived progenitor cells selected from the group consisting of a VEGFR1 inhibitor, a VLA-4 inhibitor, and an MMP-9 inhibitor under conditions effective to prevent metastases in the cancer patient. ### Claim 20 (depends on 19) The method according to claim 19, wherein said administering is carried out at a time period corresponding to when vascular endothelial growth factor receptor 1+ bone marrow-derived progenitor cell mobilization is stimulated. ### Claim 21 (depends on 20) The method according to claim 20, wherein vascular endothelial growth factor receptor 1+ bone marrow-derived progenitor cell mobilization is stimulated by chemotherapy, stress, surgery, inflammation, irradiation, or growth factors. ### Claim 22 (depends on 21) The method according to claim 21, wherein vascular endothelial growth factor receptor 1+ bone marrow-derived progenitor cell mobilization is stimulated by chemotherapy. ### Claim 23 (depends on 21) The method according to claim 21, wherein vascular endothelial growth factor receptor 1+ bone marrow-derived progenitor cell mobilization is stimulated by stress. ### Claim 24 (depends on 21) The method according to claim 21, wherein vascular endothelial growth factor receptor 1+ bone marrow-derived progenitor cell mobilization is stimulated by surgery. ### Claim 25 (depends on 21) The method according to claim 21, wherein vascular endothelial growth factor receptor 1+ bone marrow-derived progenitor cell mobilization is stimulated by mobilization of inflammatory cells. ### Claim 26 (depends on 21) The method according to claim 21, wherein vascular endothelial growth factor receptor 1+ bone marrow-derived progenitor cell mobilization is stimulated by irradiation. ### Claim 27 (depends on 21) The method according to claim 21, wherein vascular endothelial growth factor receptor 1+ bone marrow-derived progenitor cell mobilization is stimulated by growth factors. ### Claim 28 (depends on 27) The method according to claim 27, wherein the growth factors are selected from the group consisting of granulocyte colony stimulating factors, granulocyte macrophage stimulating factors, and growth hormones that stimulate bone marrow cell growth. ### Claim 29 (depends on 19) The method according to claim 19, wherein the inhibitor of vascular endothelial growth factor receptor 1+ bone marrow-derived progenitor cells binds to vascular endothelial growth factor receptor 1+ bone marrow-derived progenitor cells. ### Claim 30 (depends on 19) The method according to claim 19, wherein the inhibitor of vascular endothelial growth factor receptor 1+ bone marrow-derived progenitor cells prevents or reduces formation of vascular endothelial growth factor receptor 1+ bone marrow-derived progenitor cells. ### Claim 31 (depends on 19) The method according to claim 19, wherein the inhibitor of vascular endothelial growth factor receptor 1+ bone marrow-derived progenitor cells is a vascular endothelial growth factor receptor 1+ bone marrow-derived progenitor cell-specific antibody or antigen-binding portion thereof. ### Claim 32 (depends on 31) The method according to claim 31, wherein a polyclonal antibody is administered. ### Claim 33 (depends on 31) The method according to claim 31, wherein a monoclonal antibody is administered. ### Claim 34 (depends on 31) The method according to claim 31, wherein an antigen-binding portion of an antibody is administered. ### Claim 35 (depends on 19) The method according to claim 19, wherein the inhibitor is an antibody or an antigen-binding portion of an antibody capable of binding to VLA-4 (α4β1) integrin. ### Claim 36 (depends on 19) The method according to claim 19, wherein said administering is part of an adjuvant therapy regime. ### Claim 37 A method of preventing or inhibiting tumor formation in a cancer patient at a site remote from sites of prior tumor formation, said method comprising: selecting a cancer patient having had a primary tumor resection and having an increased blood or tissue level of vascular endothelial growth factor receptor 1+ (VEGFR1+) bone marrow derived progenitor cells compared to a prior measured level of VEGFR1+ bone marrow derived progenitor cells in the patient and administering to the selected cancer patient a VEGFR1 inhibitor, a VLA-4 inhibitor, or an MMP-9 inhibitor under conditions effective to prevent or inhibit tumor formation in the cancer patient at a site remote from sites of prior tumor formation. ### Claim 38 (depends on 37) The method according to claim 37, wherein the inhibitor is an antibody or an antigen-binding portion of an antibody capable of binding to VEGFR1. ### Claim 39 (depends on 1) The method according to claim 1, wherein the inhibitor is an antibody or an antigen-binding portion of an antibody capable of binding to VEGFR1. ### Claim 40 (depends on 19) The method according to claim 19, wherein the inhibitor is an antibody or an antigen-binding portion of an antibody capable of binding to VEGFR1.