Enhanced in vitro and in vivo cytotoxicity of umbilical cord blood cells against human breast cancer following activation with IL-15 and colony stimulating factors

Todd R. Lovgren, Stefano R. Tarantolo, Cody Evans, Charles A. Kuszynski, Shantaram S Joshi

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background: Cord blood mononuclear cells (MNC) are a rich source of precursor cytotoxic effector cells. Earlier we have shown that interleukin-2 (IL-2)-activated MNC from cord blood have significant cytotoxic activity against human leukemia and breast cancer cells in vitro and in vivo, compared to MNC from peripheral blood. Materials and methods: In order to further improve the antitumor cytotoxic ability of cord blood MNC, IL-2 was combined with IL-15 and colony stimulating factors, GMCSF, G-CSF and M-CSF for the activation. The activated cells were examined for their cytotoxic effects in vitro against human breast cancer cell lines MDA-231, MDA453 and SKB43 and in vivo against MDA-231 grown in SCID mice. Phenotypes of these activated cells were determined using flow cytometry. The expression of immune response related genes in activated cells was measured using RT-PCR techniques. Results: There was a significant increase in cytotoxicity of the effector cells activated with IL-2, IL-15 and some colony stimulating factors compared to cells activated with each of these cytokines alone or other combinations. Our results demonstrated the increase in cytotoxicity appears to be due to: 1) increase in CD56-positive cytotoxic cells; 2) cytokine/cytotoxic factors produced by the effector cells, such as Interferon-7 and Perforin; 3) stimulation by accessory cells, such as dendritic cells. In vivo administration of in vitro-activated cord blood cells into SCID mice bearing MDA-231 tumors reduced the number of metastases and increased survival compared to untreated tumor bearing controls. Conclusion: The combination of IL-2 with IL-15 and CSF is better for the activation of cord blood effector cells than to IL-2 alone.

Original languageEnglish (US)
Pages (from-to)541-550
Number of pages10
JournalIn Vivo
Volume16
Issue number6
StatePublished - Nov 1 2002

Fingerprint

Colony-Stimulating Factors
Interleukin-15
Cytotoxicity
Fetal Blood
Blood Cells
Blood
Chemical activation
Interleukin-2
Cells
Breast Neoplasms
Bearings (structural)
Macrophage Colony-Stimulating Factor
Tumors
Cytokines
SCID Mice
Perforin
Flow cytometry
Accessories
Granulocyte Colony-Stimulating Factor
Interferons

Keywords

  • Breast cancer
  • Colony stimulating factors
  • Cord blood
  • Effector cells
  • IL-15
  • Non-specific killing

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology

Cite this

Enhanced in vitro and in vivo cytotoxicity of umbilical cord blood cells against human breast cancer following activation with IL-15 and colony stimulating factors. / Lovgren, Todd R.; Tarantolo, Stefano R.; Evans, Cody; Kuszynski, Charles A.; Joshi, Shantaram S.

In: In Vivo, Vol. 16, No. 6, 01.11.2002, p. 541-550.

Research output: Contribution to journalArticle

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abstract = "Background: Cord blood mononuclear cells (MNC) are a rich source of precursor cytotoxic effector cells. Earlier we have shown that interleukin-2 (IL-2)-activated MNC from cord blood have significant cytotoxic activity against human leukemia and breast cancer cells in vitro and in vivo, compared to MNC from peripheral blood. Materials and methods: In order to further improve the antitumor cytotoxic ability of cord blood MNC, IL-2 was combined with IL-15 and colony stimulating factors, GMCSF, G-CSF and M-CSF for the activation. The activated cells were examined for their cytotoxic effects in vitro against human breast cancer cell lines MDA-231, MDA453 and SKB43 and in vivo against MDA-231 grown in SCID mice. Phenotypes of these activated cells were determined using flow cytometry. The expression of immune response related genes in activated cells was measured using RT-PCR techniques. Results: There was a significant increase in cytotoxicity of the effector cells activated with IL-2, IL-15 and some colony stimulating factors compared to cells activated with each of these cytokines alone or other combinations. Our results demonstrated the increase in cytotoxicity appears to be due to: 1) increase in CD56-positive cytotoxic cells; 2) cytokine/cytotoxic factors produced by the effector cells, such as Interferon-7 and Perforin; 3) stimulation by accessory cells, such as dendritic cells. In vivo administration of in vitro-activated cord blood cells into SCID mice bearing MDA-231 tumors reduced the number of metastases and increased survival compared to untreated tumor bearing controls. Conclusion: The combination of IL-2 with IL-15 and CSF is better for the activation of cord blood effector cells than to IL-2 alone.",
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T1 - Enhanced in vitro and in vivo cytotoxicity of umbilical cord blood cells against human breast cancer following activation with IL-15 and colony stimulating factors

AU - Lovgren, Todd R.

AU - Tarantolo, Stefano R.

AU - Evans, Cody

AU - Kuszynski, Charles A.

AU - Joshi, Shantaram S

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N2 - Background: Cord blood mononuclear cells (MNC) are a rich source of precursor cytotoxic effector cells. Earlier we have shown that interleukin-2 (IL-2)-activated MNC from cord blood have significant cytotoxic activity against human leukemia and breast cancer cells in vitro and in vivo, compared to MNC from peripheral blood. Materials and methods: In order to further improve the antitumor cytotoxic ability of cord blood MNC, IL-2 was combined with IL-15 and colony stimulating factors, GMCSF, G-CSF and M-CSF for the activation. The activated cells were examined for their cytotoxic effects in vitro against human breast cancer cell lines MDA-231, MDA453 and SKB43 and in vivo against MDA-231 grown in SCID mice. Phenotypes of these activated cells were determined using flow cytometry. The expression of immune response related genes in activated cells was measured using RT-PCR techniques. Results: There was a significant increase in cytotoxicity of the effector cells activated with IL-2, IL-15 and some colony stimulating factors compared to cells activated with each of these cytokines alone or other combinations. Our results demonstrated the increase in cytotoxicity appears to be due to: 1) increase in CD56-positive cytotoxic cells; 2) cytokine/cytotoxic factors produced by the effector cells, such as Interferon-7 and Perforin; 3) stimulation by accessory cells, such as dendritic cells. In vivo administration of in vitro-activated cord blood cells into SCID mice bearing MDA-231 tumors reduced the number of metastases and increased survival compared to untreated tumor bearing controls. Conclusion: The combination of IL-2 with IL-15 and CSF is better for the activation of cord blood effector cells than to IL-2 alone.

AB - Background: Cord blood mononuclear cells (MNC) are a rich source of precursor cytotoxic effector cells. Earlier we have shown that interleukin-2 (IL-2)-activated MNC from cord blood have significant cytotoxic activity against human leukemia and breast cancer cells in vitro and in vivo, compared to MNC from peripheral blood. Materials and methods: In order to further improve the antitumor cytotoxic ability of cord blood MNC, IL-2 was combined with IL-15 and colony stimulating factors, GMCSF, G-CSF and M-CSF for the activation. The activated cells were examined for their cytotoxic effects in vitro against human breast cancer cell lines MDA-231, MDA453 and SKB43 and in vivo against MDA-231 grown in SCID mice. Phenotypes of these activated cells were determined using flow cytometry. The expression of immune response related genes in activated cells was measured using RT-PCR techniques. Results: There was a significant increase in cytotoxicity of the effector cells activated with IL-2, IL-15 and some colony stimulating factors compared to cells activated with each of these cytokines alone or other combinations. Our results demonstrated the increase in cytotoxicity appears to be due to: 1) increase in CD56-positive cytotoxic cells; 2) cytokine/cytotoxic factors produced by the effector cells, such as Interferon-7 and Perforin; 3) stimulation by accessory cells, such as dendritic cells. In vivo administration of in vitro-activated cord blood cells into SCID mice bearing MDA-231 tumors reduced the number of metastases and increased survival compared to untreated tumor bearing controls. Conclusion: The combination of IL-2 with IL-15 and CSF is better for the activation of cord blood effector cells than to IL-2 alone.

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