Immunotherapeutic potential of dendritic cells generated in long term stroma-dependent cultures

HC O'Neill, N Jonas, H Wilson, K Ni

Research output: Contribution to journalArticleResearchpeer-review

12 Citations (Scopus)

Abstract

Long term cultures (LTC) producing dendritic cells (DC) have been established from spleen. A well developed stromal cell layer supported production of DC in numbers suitable for experimentation. Cells had obvious membrane pseudopodia and could be collected from culture every 2-3 days. Large cells produced in LTC stained with fluorescently labelled monoclonal antibodies specific for DC such as 33D1, and M1/70 which is specific for DC and myeloid cells. These staining patterns confirmed the presence of DC within the LTC population.

LTC-DC were tested and shown capable of migration in vivo in B10.A(2R) mice following footpad inoculation. Most cells entered the spleen and a small number entered popliteal lymph node. LTC-DC have migratory capacity comparable with control spleen lymphocytes. LTC-DC were tested for capacity to induce an anti-tumour immune response after exposing cells to tumour cell membranes. LTC-DC pulsed with BL/VL3 tumour antigens were able to induce a BL/VL3-specific primary cytotoxic T lymphocyte (CTL) response detectable in popliteal lymph nodes and spleen of C57BL/6J mice within 6 days of priming. BL/VL3 tumour cells grew in sublethally irradiated C57BL/6J mice giving 100% mortality. Adoptive transfer of spleen cells from mice given BL/VL3 antigen-pulsed LTC-DC, two weeks previously, significantly slowed the growth of BL/VL3 tumour cells in mice.

DC produced in LTC can function as antigen presenting cells (APC) when adoptively transferred into animals. Their capacity to migrate effectively, to induce a CTL response and to reduce tumour load suggests that DC grown using this in vitro system may have valuable clinical potential in humans.

Original languageEnglish
Pages (from-to)263-276
Number of pages14
JournalCancer Biotherapy and Radiopharmaceuticals
Volume14
Issue number4
DOIs
Publication statusPublished - Aug 1999
Externally publishedYes

Cite this

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title = "Immunotherapeutic potential of dendritic cells generated in long term stroma-dependent cultures",
abstract = "Long term cultures (LTC) producing dendritic cells (DC) have been established from spleen. A well developed stromal cell layer supported production of DC in numbers suitable for experimentation. Cells had obvious membrane pseudopodia and could be collected from culture every 2-3 days. Large cells produced in LTC stained with fluorescently labelled monoclonal antibodies specific for DC such as 33D1, and M1/70 which is specific for DC and myeloid cells. These staining patterns confirmed the presence of DC within the LTC population.LTC-DC were tested and shown capable of migration in vivo in B10.A(2R) mice following footpad inoculation. Most cells entered the spleen and a small number entered popliteal lymph node. LTC-DC have migratory capacity comparable with control spleen lymphocytes. LTC-DC were tested for capacity to induce an anti-tumour immune response after exposing cells to tumour cell membranes. LTC-DC pulsed with BL/VL3 tumour antigens were able to induce a BL/VL3-specific primary cytotoxic T lymphocyte (CTL) response detectable in popliteal lymph nodes and spleen of C57BL/6J mice within 6 days of priming. BL/VL3 tumour cells grew in sublethally irradiated C57BL/6J mice giving 100{\%} mortality. Adoptive transfer of spleen cells from mice given BL/VL3 antigen-pulsed LTC-DC, two weeks previously, significantly slowed the growth of BL/VL3 tumour cells in mice.DC produced in LTC can function as antigen presenting cells (APC) when adoptively transferred into animals. Their capacity to migrate effectively, to induce a CTL response and to reduce tumour load suggests that DC grown using this in vitro system may have valuable clinical potential in humans.",
author = "HC O'Neill and N Jonas and H Wilson and K Ni",
year = "1999",
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doi = "10.1089/cbr.1999.14.263",
language = "English",
volume = "14",
pages = "263--276",
journal = "Antibody, Immunoconjugates, and Radiopharmaceuticals",
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Immunotherapeutic potential of dendritic cells generated in long term stroma-dependent cultures. / O'Neill, HC; Jonas, N; Wilson, H; Ni, K.

In: Cancer Biotherapy and Radiopharmaceuticals, Vol. 14, No. 4, 08.1999, p. 263-276.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Immunotherapeutic potential of dendritic cells generated in long term stroma-dependent cultures

AU - O'Neill, HC

AU - Jonas, N

AU - Wilson, H

AU - Ni, K

PY - 1999/8

Y1 - 1999/8

N2 - Long term cultures (LTC) producing dendritic cells (DC) have been established from spleen. A well developed stromal cell layer supported production of DC in numbers suitable for experimentation. Cells had obvious membrane pseudopodia and could be collected from culture every 2-3 days. Large cells produced in LTC stained with fluorescently labelled monoclonal antibodies specific for DC such as 33D1, and M1/70 which is specific for DC and myeloid cells. These staining patterns confirmed the presence of DC within the LTC population.LTC-DC were tested and shown capable of migration in vivo in B10.A(2R) mice following footpad inoculation. Most cells entered the spleen and a small number entered popliteal lymph node. LTC-DC have migratory capacity comparable with control spleen lymphocytes. LTC-DC were tested for capacity to induce an anti-tumour immune response after exposing cells to tumour cell membranes. LTC-DC pulsed with BL/VL3 tumour antigens were able to induce a BL/VL3-specific primary cytotoxic T lymphocyte (CTL) response detectable in popliteal lymph nodes and spleen of C57BL/6J mice within 6 days of priming. BL/VL3 tumour cells grew in sublethally irradiated C57BL/6J mice giving 100% mortality. Adoptive transfer of spleen cells from mice given BL/VL3 antigen-pulsed LTC-DC, two weeks previously, significantly slowed the growth of BL/VL3 tumour cells in mice.DC produced in LTC can function as antigen presenting cells (APC) when adoptively transferred into animals. Their capacity to migrate effectively, to induce a CTL response and to reduce tumour load suggests that DC grown using this in vitro system may have valuable clinical potential in humans.

AB - Long term cultures (LTC) producing dendritic cells (DC) have been established from spleen. A well developed stromal cell layer supported production of DC in numbers suitable for experimentation. Cells had obvious membrane pseudopodia and could be collected from culture every 2-3 days. Large cells produced in LTC stained with fluorescently labelled monoclonal antibodies specific for DC such as 33D1, and M1/70 which is specific for DC and myeloid cells. These staining patterns confirmed the presence of DC within the LTC population.LTC-DC were tested and shown capable of migration in vivo in B10.A(2R) mice following footpad inoculation. Most cells entered the spleen and a small number entered popliteal lymph node. LTC-DC have migratory capacity comparable with control spleen lymphocytes. LTC-DC were tested for capacity to induce an anti-tumour immune response after exposing cells to tumour cell membranes. LTC-DC pulsed with BL/VL3 tumour antigens were able to induce a BL/VL3-specific primary cytotoxic T lymphocyte (CTL) response detectable in popliteal lymph nodes and spleen of C57BL/6J mice within 6 days of priming. BL/VL3 tumour cells grew in sublethally irradiated C57BL/6J mice giving 100% mortality. Adoptive transfer of spleen cells from mice given BL/VL3 antigen-pulsed LTC-DC, two weeks previously, significantly slowed the growth of BL/VL3 tumour cells in mice.DC produced in LTC can function as antigen presenting cells (APC) when adoptively transferred into animals. Their capacity to migrate effectively, to induce a CTL response and to reduce tumour load suggests that DC grown using this in vitro system may have valuable clinical potential in humans.

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DO - 10.1089/cbr.1999.14.263

M3 - Article

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SP - 263

EP - 276

JO - Antibody, Immunoconjugates, and Radiopharmaceuticals

JF - Antibody, Immunoconjugates, and Radiopharmaceuticals

SN - 1084-9785

IS - 4

ER -