Patent application EP15194078A (EP), filed 2015-11-11
Publication number: EP3167898A1
Title: METHOD FOR OBTAINING TUMOR PEPTIDES AND USES THEREOF
Abstract: The present invention refers to a method for obtaining a cell culture supernatant or a fraction thereof comprising a specific tumor antigen peptide repertoire comprising the steps of: a) exposing in suitable conditions a tumor cell culture expressing said specific tumor antigen peptide repertoire to at least one Pattern Recognition Receptor (PRR) agonist and/or to one inflammatory cytokine to increase the opening of connexin-hemichannels (CxH); b) collecting the cell culture supernatant; and c) optionally obtaining a fraction of said supernatant, wherein said supernatant comprises MHC class I and MHC class II peptides and non-classical MHC molecules (HLA-E).
IPC codes: A61K  39/    00            A I
Claims: number: 1
text: A method for obtaining a cell culture supernatant or a fraction thereof comprising a specific tumor antigen peptide repertoire comprising the steps of:
number: 2
text: A method for obtaining a specific tumor antigen peptide repertoire loaded and/or activated dendritic cell comprising the steps of:
number: 3
text: A method for obtaining an activated tumor antigen-specific CTL comprising the steps of:
number: 4
text: The method according to any one claims 2-3 wherein dendritic cells are autologous or HLA-compatible or -semi-compatible allogenic dendritic cells.
number: 5
text: The method according to any of previous claims wherein the inflammatory cytokine is gamma-IFN.
number: 6
text: The method according to any of previous claims, wherein the tumor cell is an established tumor cell line, or a combination of tumor cell lines expressing a specific tumor antigen peptide repertoire or a tumor cell isolated by a tumor affected subject.
number: 7
text: The method according to any one of the previous claims, wherein the tumor cell derives from solid or non-solid tumors, including melanoma, lung carcinoma, colorectal adenocarcinoma, prostate adenocarcinoma, sarcoma, osteosarcoma, leukemia and T cell-lymphoma and the said specific tumor antigen peptide repertoire is specific for said tumor.
number: 8
text: The method according to any one of the previous claims, wherein the PRR agonists are Gram-negative, preferably belonging to theSalmonella genus, more preferably to non virulent strains ofSalmonella genus, or Gram-positive bacteria or components thereof,
number: 9
text: The method according to claim 8 wherein Gram negative bacteria components are LPS and/or flagellin or wherein Gram positive bacteria component is Lipoteichoic acid (LTA).
number: 10
text: A supernatant or a fraction thereof obtainable by the method according to any one of claims 1 or 5-9.
number: 11
text: The supernatant of claim 10 or a fraction thereof used in combination with a therapeutic agent, preferably at least one antibody and/or chemotherapeutic and/or immune checkpoint inhibitor.
number: 12
text: The supernatant according to any one of claims 10-11, or a fraction thereof or the peptides purified by said supernatant, for use as a medicament, preferably for use in the prevention and/or treatment of tumors, more preferably as a tumor immunotherapeutic agent or as tumor vaccine.
number: 13
text: A specific tumor antigen peptide repertoire loaded and/or activated dendritic cells obtainable by the method according to any one of claims 2 or 4-9, preferably used in combination with a therapeutic agent, preferably at least one antibody and/or chemotherapeutic and/or immune checkpoint inhibitor.
number: 14
text: The specific tumor antigen peptide repertoire loaded and/or activated dendritic cells according to claim 13, for use as a medicament, preferably for use in the prevention and/or treatment of tumors, more preferably as a tumor immunotherapeutic agent or as tumor vaccine
number: 15
text: An immunogenic composition or vaccine comprising the supernatant according to any one of claims 10-11 or a fraction thereof, or the peptides purified by said supernatant and/or at least one specific tumor antigen peptide repertoire loaded and/or activated dendritic cell of claim 13 and at least one pharmaceutically acceptable carrier and/or adjuvant.
Office action: search_report, dated 2017-05-17
Rejection reasons: novelty_epc_54
Prior art cited: ref_id: WO2009040413A2
ref_type: patent
severity: background
ref_id: WO2008019366A2
ref_type: patent
severity: background
ref_id: US2009324651A1
ref_type: patent
severity: background
ref_id: WO2004050855A2
ref_type: patent
severity: background
ref_id: AU2014271235A1
ref_type: patent
severity: background
ref_id: WO2007028573A1
ref_type: patent
severity: background
ref_id: WO9815282A1
ref_type: patent
severity: background
ref_id: WO9401458A1
ref_type: patent
severity: background
ref_id: WO2009102909A2
ref_type: patent
severity: background
ref_id: WO2012017033A1
ref_type: patent
severity: background
ref_id: - CHEN, H.L. ET AL., NAT. GENET., vol. 13, 1996, pages 210 - 213
ref_type: npl
severity: background
ref_id: - EVANS, M. ET AL., J. IMMUNOL., vol. 167, 2001, pages 5420 - 5428
ref_type: npl
severity: background
ref_id: - ALIMONTI, J. ET AL., NAT. BIOTECHNOL., vol. 18, 2000, pages 515 - 520
ref_type: npl
severity: background
ref_id: - VAN HALL T ET AL., NATURE MEDICINE, vol. 12, no. 4, April 2006 (2006-04-01)
ref_type: npl
severity: background
ref_id: - DILLMAN R. ET AL., CANCER BIOTHERAPY & RADIOPHARMACEUTICALS, vol. 24, 2009, pages 311
ref_type: npl
severity: background
ref_id: - MENDOZA-NARANJO A; SALAZAR-ONFRAY ET AL., J. IMMUNOL., vol. 178, 2007, pages 6949 - 6957
ref_type: npl
severity: background
ref_id: - EUGENIN E. A.; JUAN C. SAEZ ET AL., J. IMMUNOL, vol. 170, 2003, pages 1320 - 1328
ref_type: npl
severity: background
ref_id: - ELGUETA R.; SAEZ J. ET AL., J IMMUNOL, vol. 183, no. 1, 2009, pages 277 - 84
ref_type: npl
severity: background
ref_id: - B. J. NICHOLSON, J CELL SCI, vol. 116, 15 November 2003 (2003-11-15), pages 4479
ref_type: npl
severity: background
ref_id: - B. J. NICHOLSON, J CELL SCI, vol. 116, 15 November 2003 (2003-11-15), pages 4479
ref_type: npl
severity: background
ref_id: - G. MESE; G. RICHARD; T. W. WHITE, J INVEST DERMATOL, vol. 127, November 2007 (2007-11-01), pages 2516
ref_type: npl
severity: background
ref_id: - J. NEIJSSEN; B. PANG; J. NEEFJES, PROG BIOPHYS MOL BIOL, vol. 94, May 2007 (2007-05-01), pages 207
ref_type: npl
severity: background
ref_id: - T. J. KING; J. S. BERTRAM, BIOCHIM BIOPHYS ACTA, vol. 1719, 20 December 2005 (2005-12-20), pages 146
ref_type: npl
severity: background
ref_id: - M. MESNIL; S. CRESPIN; J. L. AVANZO; M. L. ZAIDAN-DAGLI, BIOCHIM BIOPHYS ACTA, vol. 1719, 20 December 2005 (2005-12-20), pages 125
ref_type: npl
severity: background
ref_id: - T. BOPP ET AL., J EXP MED, vol. 204, 11 June 2007 (2007-06-11), pages 1303
ref_type: npl
severity: background
ref_id: - E. OVIEDO-ORTA; W. HOWARD EVANS, BIOCHIM BIOPHYS ACTA, vol. 1662, 23 March 2004 (2004-03-23), pages 102
ref_type: npl
severity: background
ref_id: - H. MATSUE ET AL., J IMMUNOL, vol. 176, 1 January 2006 (2006-01-01), pages 181
ref_type: npl
severity: background
ref_id: - J. NEIJSSEN ET AL., NATURE, vol. 434, 3 March 2005 (2005-03-03), pages 83
ref_type: npl
severity: background
ref_id: - B. PANG ET AL., J IMMUNOL, vol. 183, 15 July 2009 (2009-07-15), pages 1083
ref_type: npl
severity: background
ref_id: - MOCELLIN S; MANDRUZZATO S; BRONTE V ET AL.: "Part I: Vaccines for solid tumours.", LANCET ONCOL, vol. 5, 2004, pages 681 - 9, XP004809747, DOI: doi:10.1016/S1470-2045(04)01610-9
ref_type: npl
severity: background
ref_id: - GUERMONPREZ P; VALLADEAU J; ZITVOGEL L ET AL.: "Antigen presentation and T cell stimulation by dendritic cells", ANNU REV IMMUNOL, vol. 20, 2002, pages 621 - 67, XP009012587, DOI: doi:10.1146/annurev.immunol.20.100301.064828
ref_type: npl
severity: background
ref_id: - JANEWAY CA JR; TRAVERS P; WALPORT M ET AL.: "Immunobiology: The Immune System in Health and Disease", 2001, GARLAND SCIENCE
ref_type: npl
severity: background
ref_id: - KAWAI T; AKIRA S.: "Toll-like receptors and their crosstalk with other innate receptors in infection and immunity.", IMMUNITY, vol. 34, 2011, pages 637 - 50, XP028218505, DOI: doi:10.1016/j.immuni.2011.05.006
ref_type: npl
severity: background
ref_id: - WEBSTER RM.: "The immune checkpoint inhibitors: where are we now?", NATURE REVIEWS DRUG DISCOVERY, vol. 13, 2014, pages 883 - 884
ref_type: npl
severity: background
ref_id: - REMINGTON: "Remington: The Science and Practice of Pharmacy", 2000, LIPPINCOTT WILLIAMS & WILKINS
ref_type: npl
severity: background
ref_id: - MOCELLIN, S.: "Peptides in melanoma therapy", CURRENT PHARMACEUTICAL DESIGNL, vol. 8, no. 6, 2012, pages 820 - 831
ref_type: npl
severity: background
ref_id: - ADAMS, S.; M. A. LOWES ET AL.: "Lack of functionally active Melan-A(26-35)-specific T cells in the blood of HLA-A2+ vitiligo patients", THE JOURNAL OF INVESTIGATIVE DERMATOLOGY, vol. 128, no. 8, 2008, pages 1977 - 1980
ref_type: npl
severity: background
ref_id: - FOURCADE, J.; Z. SUN ET AL.: "Human tumor antigen-specific helper and regulatory T cells share common epitope specificity but exhibit distinct T cell repertoire", JOURNAL OF IMMUNOLOGYL, vol. 84, no. 12, 2010, pages 6709 - 6718
ref_type: npl
severity: background
ref_id: - SPEISER, D. E.; P. BAUMGAERTNER ET AL.: "Unmodified self antigen triggers human CD8 T cells with stronger tumor reactivity than altered antigen", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, vol. 105, no. 10, 2008, pages 3849 - 3854
ref_type: npl
severity: background
ref_id: - MEIJER, S. L.; A. DOLS ET AL.: "Induction of circulating tumor-reactive CD8+ T cells after vaccination of melanoma patients with the gp100 209-2M peptide", JOURNAL OF IMMUNOTHERAPY, vol. 30, no. 5, 2007, pages 533 - 543
ref_type: npl
severity: background
ref_id: - KNITTELFELDER, R.; A. B. RIEMER ET AL.: "Mimotope vaccination--from allergy to cancer", EXPERT OPINION ON BIOLOGICAL THERAPY, vol. 9, no. 4, 2009, pages 493 - 506, XP055125089, DOI: doi:10.1517/14712590902870386
ref_type: npl
severity: background
ref_id: - VAN STIPDONK, M. J.; D. BADIA-MARTINEZ ET AL.: "Design of agonistic altered peptides for the robust induction of CTL directed towards H-2Db in complex with the melanoma-associated epitope gp100", CANCER RESEARCH, vol. 69, no. 19, 2009, pages 7784 - 7792
ref_type: npl
severity: background
ref_id: - PARMIANI, G.; C. CASTELLI ET AL.: "Cancer immunotherapy with peptide-based vaccines: what have we achieved? Where are we going?", JOURNAL OF THE NATIONAL CANCER INSTITUTE, vol. 94, no. 11, 2002, pages 805 - 818, XP002435631
ref_type: npl
severity: background
ref_id: - SACCHERI, F.; C. POZZI ET AL.: "Bacteria-induced gap junctions in tumors favor antigen cross-presentation and antitumor immunity", SCIENCE TRANSLATIONAL MEDICINE, vol. 2, no. 44, 2010, pages 44RA57, XP008143049, DOI: doi:10.1126/scitranslmed.3000739
ref_type: npl
severity: background
ref_id: - SAEZ, J. C.; M. A. RETAMAL ET AL.: "Connexin-based gap junction hemichannels: gating mechanisms", BIOCHIMICA ET BIOPHYSICA ACTA, vol. L711, no. 2, 2005, pages 215 - 224, XP004933447, DOI: doi:10.1016/j.bbamem.2005.01.014
ref_type: npl
severity: background
ref_id: WO2012017033A1
ref_type: patent
severity: background
ref_id: - SACCHERI FABIANA ET AL: "Bacteria-induced gap junctions in tumors favor antigen cross-presentation and antitumor immunity", SCIENCE TRANSLATIONAL MEDICINE, AAAS - AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE, US, vol. 2, no. 44, 11 August 2010 (2010-08-11), pages 44ra57 - 1, XP008143049, ISSN: 1946-6242, DOI: 10.1126/SCITRANSLMED.3000739
ref_type: npl
severity: background
ref_id: - ARIADNA MENDOZA-NARANJO ET AL: "Functional gap junctions facilitate melanoma antigen transfer and cross-presentation between human dendritic cells", THE JOURNAL OF IMMUNOLOGY, THE AMERICAN ASSOCIATION OF IMMUNOLOGISTS, US, vol. 178, no. 11, 1 June 2007 (2007-06-01), pages 6949 - 6957, XP002659392, ISSN: 0022-1767
ref_type: npl
severity: background
ref_id: WO2012017033
ref_type: patent
severity: novelty_destroying
ref_id: - SACCHERI FABIANA ET AL, "Bacteria-induced gap junctions in tumors favor antigen cross-presentation and antitumor immunity", SCIENCE TRANSLATIONAL MEDICINE, AAAS - AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE, US, (20100811), vol. 2, no. 44, doi:10.1126/SCITRANSLMED.3000739, ISSN 1946-6242, pages 44ra57 - 1, XP008143049 [X] 1-10,13-15 * abstract * * page  1, column  r, paragraph  l  - page  2, column  r, paragraph  1 * * page  3, column  l, paragraph  2  - page  4, column  l, paragraph  1 * * page  5, column  r, paragraph  2  - page  6, column  r, paragraph  2 * [I] 11,12
ref_type: npl
severity: novelty_destroying
ref_id: - ARIADNA MENDOZA-NARANJO ET AL, "Functional gap junctions facilitate melanoma antigen transfer and cross-presentation between human dendritic cells", THE JOURNAL OF IMMUNOLOGY, THE AMERICAN ASSOCIATION OF IMMUNOLOGISTS, US, (20070601), vol. 178, no. 11, ISSN 0022-1767, pages 6949 - 6957, XP002659392 [A] 1-15 * the whole document *
ref_type: npl
severity: background
Final disposition: pending (2017-05-17)