TY - JOUR
T1 - Synergy between an antibody and CD8+ cells in eliminating an established tumor
AU - Vasović, Ljiljana V.
AU - Dyall, Ruben
AU - Clynes, Raphael A.
AU - Ravetch, Jeffrey V.
AU - Nikolić-Žugić, Janko
PY - 1997
Y1 - 1997
N2 - We investigated the effector mechanisms operating during the rejection of a transplantable solid lymphoma E.G7 (H-2b) which expresses the gene encoding chicken ovalbumin (OVA). Anti-OVA cytotoxic T lymphocytes (CTL) completely and specifically protected animals from the onset of, but could not eradicate established, E.G7 tumors. The growth of the same lymphoma was also effectively prevented by the antibody GK1.5, whose target molecule, CD4, was expressed on E.G7 cells in vivo. Furthermore, GK1.5 was able to eradicate established solid E.G7 tumors. GK1.5-mediated tumor elimination was due to its antitumor activity, and not to the elimination of regulatory CD4+ cells, based on unimpaired tumor growth in the absence of GK1.5 in animals that genetically lack CD4 T cells. In vitro, GK1.5 did not kill tumor cells: complement activation or apoptosis induction were not evident. In vivo, GK1.5-mediated tumor regression did not depend on natural killer cells, but it absolutely required CD8+ cells and intact Fcγ receptor. We conclude that, in the E.G7 model, the collaboration of antibody and CTL immunity was crucial for the successful immunotherapy of established tumors. The mechanism of this collaboration is discussed.
AB - We investigated the effector mechanisms operating during the rejection of a transplantable solid lymphoma E.G7 (H-2b) which expresses the gene encoding chicken ovalbumin (OVA). Anti-OVA cytotoxic T lymphocytes (CTL) completely and specifically protected animals from the onset of, but could not eradicate established, E.G7 tumors. The growth of the same lymphoma was also effectively prevented by the antibody GK1.5, whose target molecule, CD4, was expressed on E.G7 cells in vivo. Furthermore, GK1.5 was able to eradicate established solid E.G7 tumors. GK1.5-mediated tumor elimination was due to its antitumor activity, and not to the elimination of regulatory CD4+ cells, based on unimpaired tumor growth in the absence of GK1.5 in animals that genetically lack CD4 T cells. In vitro, GK1.5 did not kill tumor cells: complement activation or apoptosis induction were not evident. In vivo, GK1.5-mediated tumor regression did not depend on natural killer cells, but it absolutely required CD8+ cells and intact Fcγ receptor. We conclude that, in the E.G7 model, the collaboration of antibody and CTL immunity was crucial for the successful immunotherapy of established tumors. The mechanism of this collaboration is discussed.
KW - Antibody
KW - Cytotoxic T lymphocyte
KW - Lymphoma
KW - Tumor regression
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U2 - 10.1002/eji.1830270206
DO - 10.1002/eji.1830270206
M3 - Article
C2 - 9045907
AN - SCOPUS:0031045256
SN - 0014-2980
VL - 27
SP - 374
EP - 382
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 2
ER -