US2013017600A1PendingUtilityA1
Isolation and/or preservation of dendritic cells for prostate cancer immunotherapy
Assignee: NORTHWEST BIOTHERAPEUTICS INCPriority: Jul 31, 1995Filed: Jun 14, 2012Published: Jan 17, 2013
Est. expiryJul 31, 2015(expired)· nominal 20-yr term from priority
C07K 7/06C07K 14/705A61P 35/00A61P 37/04A61P 13/08A61K 40/4276A61K 40/24A61K 40/19A61K 2239/58A61K 2239/38A61K 39/001195
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Claims
Abstract
Methods and compositions for use of human dendritic cells to activate T cells for immunotherapeutic responses against primary and metastatic prostate cancer are disclosed. In one embodiment, human dendritic cells, after exposure to a prostate cancer antigen or specific antigenic peptide, are administered to a prostate cancer patient to activate the relevant T cell responses in vivo. In an alternate embodiment, human dendritic cells are exposed to a prostate cancer antigen or specific antigenic peptide in vitro and incubated or cultured with primed or unprimed T cells to activate the relevant T cell responses in vitro. The activated T cells are then administered to a prostate cancer patient. Methods and compositions for human dendritic cells with extended life span and cryopreserved dendritic cells are disclosed.
Claims
exact text as granted — not AI-modified1 . A composition comprising an isolated cell population having human dendritic cells, wherein said cell population has been cultured in the presence of granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin 4 (IL-4), and exposed in vitro to a soluble prostate antigen, the cell population having an increased ability to activate T cells specific to the prostate antigen as compared to a similar isolated cell population cultured in the presence of granulocyte-macrophage colony stimulating factor (GM-CSF), and interleukin 4 (IL-4) that has not been exposed in vitro to the prostate antigen.
2 . The composition according to claim 1 , in which the prostate antigen is a lysate of LNCaP cells, a membrane preparation of LNCaP cells, a lysate of prostate tumor cells from a prostate cancer patient, a membrane preparation of prostate tumor cells from a prostate cancer patient, isolated prostate specific membrane antigen (PSMA), purified prostate specific membrane antigen (PSMA), a peptide having the amino acid sequence LLHETDSAV (SEQ ID NO: 1), a peptide having the amino acid sequence ALFDIESKV (SEQ ID NO: 2), a peptide having the amino acid sequence XL(or M)XXXXXV(or L) (SEQ ID NO: 3), where X represents any amino acid, purified prostate specific antigen (PSA), or a purified prostate mucin antigen recognized by monoclonal antibody PD41.
3 . The composition according to claim 1 , in which the prostate antigen is selected from the group consisting of:
WLCAGALVL;
(SEQ. ID. NO. 4)
VLAGGFFLL;
(SEQ. ID. NO. 5)
ELAHYDVIA;
(SEQ. ID. NO. 6)
NLNGAGDPL;
(SEQ. ID. NO. 7)
TLRVDCTPL;
(SEQ. ID. NO. 8)
VLRMMNDQL;
(SEQ. ID. NO. 9)
PMFKYHLTV;
(SEQ. ID. NO. 10)
NMKAFLDEL;
(SEQ. ID. NO. 11)
LMYSLVHNL;
(SEQ. ID. NO. 12)
MMNDQLMFL;
(SEQ. ID. NO. 13)
EGDLVYVNY;
(SEQ. ID. NO. 14)
AGDPLTPGY;
(SEQ. ID. NO. 15)
RVDCTPLMY;
(SEQ. ID. NO. 16)
LFEPPPPGY;
(SEQ. ID. NO. 17)
TYELVEKFY;
(SEQ. ID. NO. 18)
AGESFPGIY;
(SEQ. ID. NO. 19)
WGEVKRQIY;
(SEQ. ID. NO. 20)
IVRSFGTLKKE;
(SEQ. ID. NO. 21)
DELKAENIKKF;
(SEQ. ID. NO. 22)
KSLYESWTKKS;
(SEQ. ID. NO. 23)
AYINADSSI;
(SEQ. ID. NO. 24)
KYADKIYSI;
(SEQ. ID. NO. 25)
GYYDAQKLL;
(SEQ. ID. NO. 26)
TYSVSFDSL;
(SEQ. ID. NO. 27)
NYARTEDFF;
(SEQ. ID. NO. 28)
LYSDPADYF;
(SEQ. ID. NO. 29)
LPSIPVHPI;
(SEQ. ID. NO. 30)
SPSPEFSGM;
(SEQ. ID. NO. 31)
VLVHPQWUL;
(SEQ. ID. NO. 32)
KLQCVDLHV;
(SEQ. ID. NO. 33)
ALPERPSLY;
(SEQ. ID. NO. 34)
JVGGWECEK;
(SEQ. ID. NO. 35)
QVHPQKVTK;
(SEQ. ID. NO. 36)
VVHYRKWIK;
(SEQ. ID. NO. 37)
CYASGWGSI.
(SEQ. ID. NO. 38)
4 . The composition according to claim 1 , in which the dendritic cells are extended life span dendritic cells.
5 . The composition according to claim 1 , in which the prostate tissue antigen is:
WLCAGALVL;
(SEQ. ID. NO. 4)
VLAGGFFLL;
(SEQ. ID. NO. 5)
ELAHYDVLL;
(SEQ. ID. NO. 6)
NLNGAGDPL;
(SEQ. ID. NO. 7)
TLRVDCTPL;
(SEQ. ID. NO. 8)
VLRMMNDQL;
(SEQ. ID. NO. 9)
PMFKYHLTV;
(SEQ. ID. NO. 10)
NMKAFLDEL;
(SEQ. ID. NO. 11)
LMYSLVHNL;
(SEQ. ID. NO. 12)
MMNDQLMFL;
(SEQ. ID. NO. 13)
EGDLVYVNY;
(SEQ. ID. NO. 14)
AGDPLTPGY;
(SEQ. ID. NO. 15)
RVDCTPLMY;
(SEQ. ID. NO. 16)
LFEPPPPGY;
(SEQ. ID. NO. 17)
TYELVEKFY;
(SEQ. ID. NO. 18)
AGESFPGIY;
(SEQ. ID. NO. 19)
WGEVKRQIY;
(SEQ. ID. NO. 20)
IVRSFGTLKKE;
(SEQ. ID. NO. 21)
DELKAENIKKF;
(SEQ. ID. NO. 22)
KSLYESWTKKS;
(SEQ. ID. NO. 23)
AYINADSSI;
(SEQ. ID. NO. 24)
KYADKIYSI;
(SEQ. ID. NO. 25)
GYYDAQKLL;
(SEQ. ID. NO. 26)
TYSVSFDSL;
(SEQ. ID. NO. 27)
NYARTEDFF;
(SEQ. ID. NO. 28)
LYSDPADYF;
(SEQ. ID. NO. 29)
LPSIPVHPI;
(SEQ. ID. NO. 30)
SPSPEFSGM;
(SEQ. ID, NO. 31)
VLVHPQWUL;
(SEQ. ID. NO. 32)
KLQCVDLHV;
(SEQ. ID. NO. 33)
ALPERPSLY;
(SEQ. ID. NO. 34)
JVGGWECEK;
(SEQ. ID. NO. 35)
QVHPQKVTK;
(SEQ. ID. NO. 36)
VVHYRKWIK;
(SEQ. ID. NO. 37)
or
CYASGWGSI.
(SEQ. ID. NO. 38)
6 . The composition according to claim 1 , in which the dendritic cells have been cryopreserved prior to exposure in vitro to the prostate antigen, wherein said dendritic cells retain the ability to take up and present antigen.
7 . The composition according to claim 6 , in which the prostate antigen is a lysate of LNCaP cells, a membrane preparation of LNCaP cells, a lysate of prostate tumor cells from a prostate cancer patient, a membrane preparation of prostate tumor cells from a prostate cancer patient, isolated prostate specific membrane antigen (PSMA), purified prostate specific membrane antigen (PSMA), a peptide having the amino acid sequence LLHETDSAV (SEQ. ID. NO. 1), a peptide having the amino acid sequence ALFDIESKV (SEQ. ID. NO. 2), a peptide having the amino acid sequence XL(or M)XXXXXV(or L) (SEQ. ID. NO. 3), where X represents any amino acid, purified prostate specific antigen (PSA), or a purified prostate mucin antigen recognized by monoclonal antibody PD41.
8 . The composition according to claim 6 , in which the dendritic cells are extended life dendritic cells.
9 . The composition according to claim 1 , wherein said dendritic cells can activate 2 to 3 fold more T cells specific to the prostate antigen as compared to an isolated cell population cultured in the presence of granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin 4 (IL-4) that has not been exposed in vitro to the prostate antigen.
10 . The composition according to claim 1 , wherein the human dendritic cells are immature dendritic cells.
11 . The composition according to claim 1 , wherein the T cells are CD4 + .
12 . The composition according to claim 1 , wherein the T cells are CD8 + .
13 . The composition according to claim 1 , wherein the dendritic cells are isolated from a prostate cancer patient.
14 . The composition according to claim 1 , wherein the dendritic cells are isolated from a normal individual.
15 . The composition according to claim 14 , wherein the dendritic cells are HLA-matched for a recipient.Cited by (0)
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