Rapid accumulation of adoptively transferred CD8+ T cells at the tumor site is associated with long-term control of SV40 T antigen-induced tumors

Jodi L. Yorty, Satvir S. Tevethia, Todd Schell

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

We previously established a model to study CD8+ T cell (T CD8)-based adoptive immunotherapy of cancer using line SV11 mice that develop choroid plexus tumors in the brain due to transgenic expression of Simian Virus 40 large T antigen (Tag). These mice are tolerant to the three dominant TCD8-recognized Tag epitopes I, II/III and IV. However, adoptive transfer of spleen cells from naïve C57BL/6 (B6) mice prolongs SV11 survival following TCD8 priming against the endogenous Tag epitope IV. In addition, survival of SV11 mice is dramatically increased following transfer of lymphocytes from Tag-immune B6 mice. In the current study, we compared the kinetics and magnitude of Tag-specific TCD8 accumulation at the tumor site following adoptive transfer with a high dose of either Tag-immune or naïve donor cells or decreasing doses of Tag-immune lymphocytes. Following adoptive transfer of Tag-immune cells, epitope I- and IV-specific TCD8 accumulated to high levels in the brain of SV11 mice, peaking at 5-7 days, while epitope IV-specific TCD8 derived from naïve donors required three weeks to achieve peak levels. A similar delay in the peak of epitope IV-specific TCD8 accumulation was observed when tenfold fewer Tag-immune donor cells were administered, reducing control of tumor progression. These results suggest that efficient and prolonged control of established autochthonous tumors is associated with high-level early accumulation of adoptively transferred T cells. We also provide evidence that although multiple specificities are represented in the Tag immune donor lymphocytes, epitope IV-specific donor TCD8 play a predominant role in control of tumor growth.

Original languageEnglish (US)
Pages (from-to)883-895
Number of pages13
JournalCancer Immunology, Immunotherapy
Volume57
Issue number6
DOIs
StatePublished - Jun 1 2008

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Polyomavirus Transforming Antigens
Viral Tumor Antigens
T-Lymphocytes
Epitopes
Neoplasms
Adoptive Transfer
Lymphocytes
Choroid Plexus Neoplasms
Adoptive Immunotherapy
Simian virus 40
Brain
Spleen

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

Cite this

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title = "Rapid accumulation of adoptively transferred CD8+ T cells at the tumor site is associated with long-term control of SV40 T antigen-induced tumors",
abstract = "We previously established a model to study CD8+ T cell (T CD8)-based adoptive immunotherapy of cancer using line SV11 mice that develop choroid plexus tumors in the brain due to transgenic expression of Simian Virus 40 large T antigen (Tag). These mice are tolerant to the three dominant TCD8-recognized Tag epitopes I, II/III and IV. However, adoptive transfer of spleen cells from na{\"i}ve C57BL/6 (B6) mice prolongs SV11 survival following TCD8 priming against the endogenous Tag epitope IV. In addition, survival of SV11 mice is dramatically increased following transfer of lymphocytes from Tag-immune B6 mice. In the current study, we compared the kinetics and magnitude of Tag-specific TCD8 accumulation at the tumor site following adoptive transfer with a high dose of either Tag-immune or na{\"i}ve donor cells or decreasing doses of Tag-immune lymphocytes. Following adoptive transfer of Tag-immune cells, epitope I- and IV-specific TCD8 accumulated to high levels in the brain of SV11 mice, peaking at 5-7 days, while epitope IV-specific TCD8 derived from na{\"i}ve donors required three weeks to achieve peak levels. A similar delay in the peak of epitope IV-specific TCD8 accumulation was observed when tenfold fewer Tag-immune donor cells were administered, reducing control of tumor progression. These results suggest that efficient and prolonged control of established autochthonous tumors is associated with high-level early accumulation of adoptively transferred T cells. We also provide evidence that although multiple specificities are represented in the Tag immune donor lymphocytes, epitope IV-specific donor TCD8 play a predominant role in control of tumor growth.",
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Rapid accumulation of adoptively transferred CD8+ T cells at the tumor site is associated with long-term control of SV40 T antigen-induced tumors. / Yorty, Jodi L.; Tevethia, Satvir S.; Schell, Todd.

In: Cancer Immunology, Immunotherapy, Vol. 57, No. 6, 01.06.2008, p. 883-895.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Rapid accumulation of adoptively transferred CD8+ T cells at the tumor site is associated with long-term control of SV40 T antigen-induced tumors

AU - Yorty, Jodi L.

AU - Tevethia, Satvir S.

AU - Schell, Todd

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N2 - We previously established a model to study CD8+ T cell (T CD8)-based adoptive immunotherapy of cancer using line SV11 mice that develop choroid plexus tumors in the brain due to transgenic expression of Simian Virus 40 large T antigen (Tag). These mice are tolerant to the three dominant TCD8-recognized Tag epitopes I, II/III and IV. However, adoptive transfer of spleen cells from naïve C57BL/6 (B6) mice prolongs SV11 survival following TCD8 priming against the endogenous Tag epitope IV. In addition, survival of SV11 mice is dramatically increased following transfer of lymphocytes from Tag-immune B6 mice. In the current study, we compared the kinetics and magnitude of Tag-specific TCD8 accumulation at the tumor site following adoptive transfer with a high dose of either Tag-immune or naïve donor cells or decreasing doses of Tag-immune lymphocytes. Following adoptive transfer of Tag-immune cells, epitope I- and IV-specific TCD8 accumulated to high levels in the brain of SV11 mice, peaking at 5-7 days, while epitope IV-specific TCD8 derived from naïve donors required three weeks to achieve peak levels. A similar delay in the peak of epitope IV-specific TCD8 accumulation was observed when tenfold fewer Tag-immune donor cells were administered, reducing control of tumor progression. These results suggest that efficient and prolonged control of established autochthonous tumors is associated with high-level early accumulation of adoptively transferred T cells. We also provide evidence that although multiple specificities are represented in the Tag immune donor lymphocytes, epitope IV-specific donor TCD8 play a predominant role in control of tumor growth.

AB - We previously established a model to study CD8+ T cell (T CD8)-based adoptive immunotherapy of cancer using line SV11 mice that develop choroid plexus tumors in the brain due to transgenic expression of Simian Virus 40 large T antigen (Tag). These mice are tolerant to the three dominant TCD8-recognized Tag epitopes I, II/III and IV. However, adoptive transfer of spleen cells from naïve C57BL/6 (B6) mice prolongs SV11 survival following TCD8 priming against the endogenous Tag epitope IV. In addition, survival of SV11 mice is dramatically increased following transfer of lymphocytes from Tag-immune B6 mice. In the current study, we compared the kinetics and magnitude of Tag-specific TCD8 accumulation at the tumor site following adoptive transfer with a high dose of either Tag-immune or naïve donor cells or decreasing doses of Tag-immune lymphocytes. Following adoptive transfer of Tag-immune cells, epitope I- and IV-specific TCD8 accumulated to high levels in the brain of SV11 mice, peaking at 5-7 days, while epitope IV-specific TCD8 derived from naïve donors required three weeks to achieve peak levels. A similar delay in the peak of epitope IV-specific TCD8 accumulation was observed when tenfold fewer Tag-immune donor cells were administered, reducing control of tumor progression. These results suggest that efficient and prolonged control of established autochthonous tumors is associated with high-level early accumulation of adoptively transferred T cells. We also provide evidence that although multiple specificities are represented in the Tag immune donor lymphocytes, epitope IV-specific donor TCD8 play a predominant role in control of tumor growth.

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