Dendritic cell-tumor cell fusion and staphylococcal enterotoxin B treatment in a pancreatic tumor model

Elizabeth J. McConnell, Latha B. Pathangey, Cathy S. Madsen, Sandra J Gendler, Pinku Mukherjee

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Background. Surgical resection of pancreatic tumors removes gross disease but not metastases. Adjuvant therapy such as chemotherapy and radiation treatment is of little value in metastatic pancreatic cancer. The hypothesis of this investigation is that specific and effective immunotherapeutic vaccine (dendritic/tumor cell fusion) will activate cytotoxic T lymphocytes (CTLs), leading to the eradication of spontaneous pancreatic cancer. Methods. We have developed a double transgenic mouse model (MET) that forms spontaneous pancreatic tumors and expresses the human MUC1 antigen. Seven-week-old MET mice (n = 8) were treated every 3 weeks with the vaccine. In addition, these mice received 50 μg of superantigen staphylococcal enterotoxin B (SEB), a known T cell stimulant, prior to the first vaccination. A second treatment group received SEB alone (n = 8) and controls received no treatment (n = 9). MUC1-specific CTLs were measured by chromium release assay. At 10 weeks of age and at necropsy, MUC1 serum levels were measured using a MUC1-specific ELISA. Results. Mice were known to harbor microscopic foci of cancer at birth. Survival was enhanced in vaccine as well as SEB-treated mice (75% CI ± 0.42) compared to controls (11% CI ± 0.28) and both groups of treated mice exhibited mature CTLs without in vitro stimulation. MUC1 serum levels of the vaccine group were 50% less than that of control (P < 0.04) at 10 weeks. MUC1 serum levels directly correlated with tumor weight at necropsy (r = √0.86). Conclusions. This is the first evidence that MUC1-specific CTLs can be stimulated to enhance survival in a spontaneous tumor model.

Original languageEnglish (US)
Pages (from-to)196-202
Number of pages7
JournalJournal of Surgical Research
Volume107
Issue number2
DOIs
StatePublished - 2002

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Cell Fusion
Dendritic Cells
Cytotoxic T-Lymphocytes
Vaccines
Neoplasms
Pancreatic Neoplasms
Serum
Therapeutics
Superantigens
Cancer Vaccines
Survival
Chromium
Tumor Burden
Transgenic Mice
Vaccination
Enzyme-Linked Immunosorbent Assay
staphylococcal enterotoxin B
Parturition
Radiation
Neoplasm Metastasis

Keywords

  • Cytotoxic T lymphocyte
  • Dendritic cells
  • Mouse model
  • MUC1
  • Pancreas
  • Spontaneous tumor

ASJC Scopus subject areas

  • Surgery

Cite this

Dendritic cell-tumor cell fusion and staphylococcal enterotoxin B treatment in a pancreatic tumor model. / McConnell, Elizabeth J.; Pathangey, Latha B.; Madsen, Cathy S.; Gendler, Sandra J; Mukherjee, Pinku.

In: Journal of Surgical Research, Vol. 107, No. 2, 2002, p. 196-202.

Research output: Contribution to journalArticle

McConnell, Elizabeth J. ; Pathangey, Latha B. ; Madsen, Cathy S. ; Gendler, Sandra J ; Mukherjee, Pinku. / Dendritic cell-tumor cell fusion and staphylococcal enterotoxin B treatment in a pancreatic tumor model. In: Journal of Surgical Research. 2002 ; Vol. 107, No. 2. pp. 196-202.
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abstract = "Background. Surgical resection of pancreatic tumors removes gross disease but not metastases. Adjuvant therapy such as chemotherapy and radiation treatment is of little value in metastatic pancreatic cancer. The hypothesis of this investigation is that specific and effective immunotherapeutic vaccine (dendritic/tumor cell fusion) will activate cytotoxic T lymphocytes (CTLs), leading to the eradication of spontaneous pancreatic cancer. Methods. We have developed a double transgenic mouse model (MET) that forms spontaneous pancreatic tumors and expresses the human MUC1 antigen. Seven-week-old MET mice (n = 8) were treated every 3 weeks with the vaccine. In addition, these mice received 50 μg of superantigen staphylococcal enterotoxin B (SEB), a known T cell stimulant, prior to the first vaccination. A second treatment group received SEB alone (n = 8) and controls received no treatment (n = 9). MUC1-specific CTLs were measured by chromium release assay. At 10 weeks of age and at necropsy, MUC1 serum levels were measured using a MUC1-specific ELISA. Results. Mice were known to harbor microscopic foci of cancer at birth. Survival was enhanced in vaccine as well as SEB-treated mice (75{\%} CI ± 0.42) compared to controls (11{\%} CI ± 0.28) and both groups of treated mice exhibited mature CTLs without in vitro stimulation. MUC1 serum levels of the vaccine group were 50{\%} less than that of control (P < 0.04) at 10 weeks. MUC1 serum levels directly correlated with tumor weight at necropsy (r = √0.86). Conclusions. This is the first evidence that MUC1-specific CTLs can be stimulated to enhance survival in a spontaneous tumor model.",
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AB - Background. Surgical resection of pancreatic tumors removes gross disease but not metastases. Adjuvant therapy such as chemotherapy and radiation treatment is of little value in metastatic pancreatic cancer. The hypothesis of this investigation is that specific and effective immunotherapeutic vaccine (dendritic/tumor cell fusion) will activate cytotoxic T lymphocytes (CTLs), leading to the eradication of spontaneous pancreatic cancer. Methods. We have developed a double transgenic mouse model (MET) that forms spontaneous pancreatic tumors and expresses the human MUC1 antigen. Seven-week-old MET mice (n = 8) were treated every 3 weeks with the vaccine. In addition, these mice received 50 μg of superantigen staphylococcal enterotoxin B (SEB), a known T cell stimulant, prior to the first vaccination. A second treatment group received SEB alone (n = 8) and controls received no treatment (n = 9). MUC1-specific CTLs were measured by chromium release assay. At 10 weeks of age and at necropsy, MUC1 serum levels were measured using a MUC1-specific ELISA. Results. Mice were known to harbor microscopic foci of cancer at birth. Survival was enhanced in vaccine as well as SEB-treated mice (75% CI ± 0.42) compared to controls (11% CI ± 0.28) and both groups of treated mice exhibited mature CTLs without in vitro stimulation. MUC1 serum levels of the vaccine group were 50% less than that of control (P < 0.04) at 10 weeks. MUC1 serum levels directly correlated with tumor weight at necropsy (r = √0.86). Conclusions. This is the first evidence that MUC1-specific CTLs can be stimulated to enhance survival in a spontaneous tumor model.

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