TY - JOUR
T1 - Amplification of tumor immunity by gene transfer of the co-stimulatory 4-1BB ligand
T2 - Synergy with the CD28 co-stimulatory pathway
AU - Melero, Ignacio
AU - Bach, Nathan
AU - Hellström, Karl Erik
AU - Aruffo, Alejandro
AU - Mittler, Robert S.
AU - Chen, Lieping
PY - 1998/3
Y1 - 1998/3
N2 - We have explored the role of an activation-induced T cell molecule, 4-1BB (CDw137), in the amplification of tumor immunity by retrovirus-mediated transduction of the 4-1BB ligand (4-1BBL) into tumor cells. Mice inoculated with P815 tumor cells expressing 4-1BBL developed a strong cytotoxic T lymphocyte (CTL) response and long-term immunity against wild-type tumor. The optimal effect of 4-1BBL in CTL stimulation required B7-CD28 interaction since blockade of this interaction by antibodies down-regulated the expression of 4-1BB on T cells and decreased CTL activity. Furthermore, co-expression of 4-1BBL and B7-1 in the poorly immunogenic AG104A sarcoma enhanced the induction of effector CTL and the rejection of the wild-type tumor while neither 4-1BBL nor B7-1 single transfectants were effective, suggesting a synergistic effect between the 4-1BB and the CD28 co-stimulatory pathways. Our results underscore the importance of the 4-1BB T cell stimulation pathway in the amplification of an antitumor immune response.
AB - We have explored the role of an activation-induced T cell molecule, 4-1BB (CDw137), in the amplification of tumor immunity by retrovirus-mediated transduction of the 4-1BB ligand (4-1BBL) into tumor cells. Mice inoculated with P815 tumor cells expressing 4-1BBL developed a strong cytotoxic T lymphocyte (CTL) response and long-term immunity against wild-type tumor. The optimal effect of 4-1BBL in CTL stimulation required B7-CD28 interaction since blockade of this interaction by antibodies down-regulated the expression of 4-1BB on T cells and decreased CTL activity. Furthermore, co-expression of 4-1BBL and B7-1 in the poorly immunogenic AG104A sarcoma enhanced the induction of effector CTL and the rejection of the wild-type tumor while neither 4-1BBL nor B7-1 single transfectants were effective, suggesting a synergistic effect between the 4-1BB and the CD28 co-stimulatory pathways. Our results underscore the importance of the 4-1BB T cell stimulation pathway in the amplification of an antitumor immune response.
KW - Co-stimulatory molecule
KW - Cytotoxic T lymphocyte
KW - Gene therapy
KW - Tumor immunity
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U2 - 10.1002/(SICI)1521-4141(199803)28:03<1116::AID-IMMU1116>3.0.CO;2-A
DO - 10.1002/(SICI)1521-4141(199803)28:03<1116::AID-IMMU1116>3.0.CO;2-A
M3 - Article
C2 - 9541607
AN - SCOPUS:0031906785
SN - 0014-2980
VL - 28
SP - 1116
EP - 1121
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 3
ER -