Tumor Cell Surface Expression of Granulocyte-Macrophage Colony-Stimulating Factor Elicits Antitumor Immunity and Protects from Tumor Challenge in the P815 Mouse Mastocytoma Tumor Model

A novel membrane-bound form of GM-CSF (mbGM-CSF) was expressed on the surface of the mouse mastocytoma cell line P815 to target tumor cell-associated Ags to epidermal Langerhans cells. Transfected clones stimulated the proliferation of syngeneic bone marrow cells, indicating that mbGM-CSF is biologi...

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Veröffentlicht in:The Journal of immunology (1950) 1999-06, Vol.162 (12), p.7343-7349
Hauptverfasser: Soo Hoo, William, Lundeen, Katherine A, Kohrumel, Joshua R, Pham, Nhat-Long, Brostoff, Steven W, Bartholomew, Richard M, Carlo, Dennis J
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container_end_page 7349
container_issue 12
container_start_page 7343
container_title The Journal of immunology (1950)
container_volume 162
creator Soo Hoo, William
Lundeen, Katherine A
Kohrumel, Joshua R
Pham, Nhat-Long
Brostoff, Steven W
Bartholomew, Richard M
Carlo, Dennis J
description A novel membrane-bound form of GM-CSF (mbGM-CSF) was expressed on the surface of the mouse mastocytoma cell line P815 to target tumor cell-associated Ags to epidermal Langerhans cells. Transfected clones stimulated the proliferation of syngeneic bone marrow cells, indicating that mbGM-CSF is biologically active. We evaluated the in vivo effects of mbGM-CSF by comparing the growth of mbGM-CSF cells (termed 1D6.1E5) to that of wild-type P815 cells in DBA/2 mice. The growth rates of tumors initiated by P815 and 1D6.1E5 were similar until day 12, after which P815 tumors grew to large sizes while 1D6. 1E5 tumors were rejected. In contrast, the growth of both tumors was unimpeded when injected into nude mice, suggesting that a T cell-dependent antitumor response was induced by 1D6.1E5 in normal mice. Lymphocytes from 1D6.1E5-vaccinated mice were able to kill 51Cr-labeled P815 cells in a dose-dependent fashion that was inhibited by anti-CD8 Abs, suggesting that the antitumor response involved CD8+ CTL. We then tested whether vaccination with these cells would elicit a protective antitumor response by injecting mice with either irradiated 1D6.1E5 or P815 cells and challenging them with nonirradiated P815 cells. 1D6.1E5-treated mice grew small tumors that soon disappeared in all animals. In contrast, the majority of animals receiving the irradiated wild-type tumor vaccine grew large tumors, and 50% died. These data demonstrate that mbGM-CSF expressed on the surface of tumor cells is biologically active and elicits protective antitumor immunity.
doi_str_mv 10.4049/jimmunol.162.12.7343
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We then tested whether vaccination with these cells would elicit a protective antitumor response by injecting mice with either irradiated 1D6.1E5 or P815 cells and challenging them with nonirradiated P815 cells. 1D6.1E5-treated mice grew small tumors that soon disappeared in all animals. In contrast, the majority of animals receiving the irradiated wild-type tumor vaccine grew large tumors, and 50% died. 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Transfected clones stimulated the proliferation of syngeneic bone marrow cells, indicating that mbGM-CSF is biologically active. We evaluated the in vivo effects of mbGM-CSF by comparing the growth of mbGM-CSF cells (termed 1D6.1E5) to that of wild-type P815 cells in DBA/2 mice. The growth rates of tumors initiated by P815 and 1D6.1E5 were similar until day 12, after which P815 tumors grew to large sizes while 1D6. 1E5 tumors were rejected. In contrast, the growth of both tumors was unimpeded when injected into nude mice, suggesting that a T cell-dependent antitumor response was induced by 1D6.1E5 in normal mice. Lymphocytes from 1D6.1E5-vaccinated mice were able to kill 51Cr-labeled P815 cells in a dose-dependent fashion that was inhibited by anti-CD8 Abs, suggesting that the antitumor response involved CD8+ CTL. 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subjects Animals
Bone Marrow Cells - pathology
Cancer Vaccines - immunology
Cell Division - genetics
Cell Division - immunology
Cell Membrane - immunology
Cell Membrane - metabolism
Clone Cells - radiation effects
Clone Cells - transplantation
Female
Genetic Vectors - chemical synthesis
Graft Rejection - genetics
Graft Rejection - immunology
Graft Rejection - pathology
Granulocyte-Macrophage Colony-Stimulating Factor - biosynthesis
Granulocyte-Macrophage Colony-Stimulating Factor - genetics
Granulocyte-Macrophage Colony-Stimulating Factor - metabolism
Immunocompromised Host
Mast-Cell Sarcoma - metabolism
Mast-Cell Sarcoma - pathology
Membrane Proteins - biosynthesis
Membrane Proteins - genetics
Mice
Mice, Inbred BALB C
Mice, Inbred DBA
Mice, Nude
Neoplasm Transplantation
T-Lymphocytes, Cytotoxic - immunology
Tumor Cells, Cultured
title Tumor Cell Surface Expression of Granulocyte-Macrophage Colony-Stimulating Factor Elicits Antitumor Immunity and Protects from Tumor Challenge in the P815 Mouse Mastocytoma Tumor Model
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