The role of B7 costimulation by murine acute myeloid leukemia in the generation and function of a CD8+T-cell line with potent in vivo graft-versus-leukemia properties

Michael W. Boyer, Daniel A. Vallera, Patricia A. Taylor, Gary S. Gray, Emmanuel Katsanis, Keith Gorden, Paul J. Orchard, Bruce R. Blazar

Research output: Contribution to journalArticle

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Abstract

Relapse is more frequent after autologous than allogeneic bone marrow transplantation (BMT), due in part to lack of T-lymphocyte mediated allogeneic graft-versus-leukemia (GVL) effects. Infusions of leukemia-reactive T cells to patients after autologous BMT may be a means for providing a GVL effect. Costimulation of T cells by binding of the CD28 receptor on T cells with B7-counter receptors on antigen presenting cells amplifies antigen-specific T-cell responses. To enhance generation of leukemia reactive cytotoxic T lymphocytes (CTL), the murine B7-1- and B7-2-costimulatory molecule cDNAs were introduced into the MHC class I+, class II, murine meyloid leukemia cell line C1498. B7-1 expression greatly enhanced the ability of the leukemia cells to generate and expand leukemia reactive CTL in vitro. A highly cytolytic and C1498 specific CDS+ CTL line was generated by B7-1 costimulation. This CTL line proliferated autonomously and produced interleukin-2 when provided B7-1 or B7-2 costimulation by C1498 leukemia cells. To test the in vivo antileukemia properties of this CTL line, irradiated syngeneic BMT recipients were given graded doses of leukemia cells on day 0, followed by CTL infusions beginning on day 1 post-BMT. Recipients of 107 CTL had a 3 log reduction in leukemia burden such that 100% of mice were protected from a supralethal leukemic cell dose. Sustained immune responses were detectable up to 3 months postinfusion of the CTL line. B71 or B7-2 costimulation in vivo did not augment antileukemia effects of infused CTL post BMT. These results suggest that B7 costimulation of leukemia reactive CTL may be important for their ex vivo generation and expansion for use in human adoptive immunotherapy of leukemia.

Original languageEnglish (US)
Pages (from-to)3477-3485
Number of pages9
JournalBlood
Volume89
Issue number9
StatePublished - 1997
Externally publishedYes

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T-cells
Cytotoxic T-Lymphocytes
Acute Myeloid Leukemia
Grafts
Leukemia
T-Lymphocytes
Transplants
Cell Line
Bone Marrow Transplantation
Bone
CD86 Antigens
Isogeneic Transplantation
T-Cell Leukemia
Adoptive Immunotherapy
Autologous Transplantation
Homologous Transplantation
Antigen-Presenting Cells
T-Cell Antigen Receptor
Interleukin-2
Complementary DNA

ASJC Scopus subject areas

  • Hematology

Cite this

The role of B7 costimulation by murine acute myeloid leukemia in the generation and function of a CD8+T-cell line with potent in vivo graft-versus-leukemia properties. / Boyer, Michael W.; Vallera, Daniel A.; Taylor, Patricia A.; Gray, Gary S.; Katsanis, Emmanuel; Gorden, Keith; Orchard, Paul J.; Blazar, Bruce R.

In: Blood, Vol. 89, No. 9, 1997, p. 3477-3485.

Research output: Contribution to journalArticle

Boyer, MW, Vallera, DA, Taylor, PA, Gray, GS, Katsanis, E, Gorden, K, Orchard, PJ & Blazar, BR 1997, 'The role of B7 costimulation by murine acute myeloid leukemia in the generation and function of a CD8+T-cell line with potent in vivo graft-versus-leukemia properties', Blood, vol. 89, no. 9, pp. 3477-3485.
Boyer, Michael W. ; Vallera, Daniel A. ; Taylor, Patricia A. ; Gray, Gary S. ; Katsanis, Emmanuel ; Gorden, Keith ; Orchard, Paul J. ; Blazar, Bruce R. / The role of B7 costimulation by murine acute myeloid leukemia in the generation and function of a CD8+T-cell line with potent in vivo graft-versus-leukemia properties. In: Blood. 1997 ; Vol. 89, No. 9. pp. 3477-3485.
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abstract = "Relapse is more frequent after autologous than allogeneic bone marrow transplantation (BMT), due in part to lack of T-lymphocyte mediated allogeneic graft-versus-leukemia (GVL) effects. Infusions of leukemia-reactive T cells to patients after autologous BMT may be a means for providing a GVL effect. Costimulation of T cells by binding of the CD28 receptor on T cells with B7-counter receptors on antigen presenting cells amplifies antigen-specific T-cell responses. To enhance generation of leukemia reactive cytotoxic T lymphocytes (CTL), the murine B7-1- and B7-2-costimulatory molecule cDNAs were introduced into the MHC class I+, class II, murine meyloid leukemia cell line C1498. B7-1 expression greatly enhanced the ability of the leukemia cells to generate and expand leukemia reactive CTL in vitro. A highly cytolytic and C1498 specific CDS+ CTL line was generated by B7-1 costimulation. This CTL line proliferated autonomously and produced interleukin-2 when provided B7-1 or B7-2 costimulation by C1498 leukemia cells. To test the in vivo antileukemia properties of this CTL line, irradiated syngeneic BMT recipients were given graded doses of leukemia cells on day 0, followed by CTL infusions beginning on day 1 post-BMT. Recipients of 107 CTL had a 3 log reduction in leukemia burden such that 100{\%} of mice were protected from a supralethal leukemic cell dose. Sustained immune responses were detectable up to 3 months postinfusion of the CTL line. B71 or B7-2 costimulation in vivo did not augment antileukemia effects of infused CTL post BMT. These results suggest that B7 costimulation of leukemia reactive CTL may be important for their ex vivo generation and expansion for use in human adoptive immunotherapy of leukemia.",
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