TY - JOUR
T1 - Homodimerization of tumor-reactive monoclonal antibodies markedly increases their ability to induce growth arrest or apoptosis of tumor cells
AU - Ghetie, Maria Ana
AU - Podar, Erika M.
AU - Ilgen, Amy
AU - Gordon, Brian E.
AU - Uhr, Jonathan W.
AU - Vitetta, Ellen S.
PY - 1997/7/8
Y1 - 1997/7/8
N2 - Monoclonal antibodies (mAbs) that exert antitumor activity can do so by virtue of their effector function and/or their ability to signal growth arrest or cell death. In this study, we demonstrate that mAbs which have little or no signaling activity-i.e., anti-CD19, CD20, CD21, CD22 and Her-2- can become potent antitumor agents when they are converted into IgG-IgG homodimers. The homodimers exert antigrowth activity by signaling G0/G1 arrest or apoptosis, depending upon which cell surface molecule they bind. This activity is specific and, in the case of the anti-CD19 mAb, did not require an Fc portion. These results offer the possibility that homodimers of other tumor-reactive mAbs which have little antitumor activity as monomers might be potent, anti-tumor agents.
AB - Monoclonal antibodies (mAbs) that exert antitumor activity can do so by virtue of their effector function and/or their ability to signal growth arrest or cell death. In this study, we demonstrate that mAbs which have little or no signaling activity-i.e., anti-CD19, CD20, CD21, CD22 and Her-2- can become potent antitumor agents when they are converted into IgG-IgG homodimers. The homodimers exert antigrowth activity by signaling G0/G1 arrest or apoptosis, depending upon which cell surface molecule they bind. This activity is specific and, in the case of the anti-CD19 mAb, did not require an Fc portion. These results offer the possibility that homodimers of other tumor-reactive mAbs which have little antitumor activity as monomers might be potent, anti-tumor agents.
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U2 - 10.1073/pnas.94.14.7509
DO - 10.1073/pnas.94.14.7509
M3 - Article
C2 - 9207122
AN - SCOPUS:0030806221
SN - 0027-8424
VL - 94
SP - 7509
EP - 7514
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 14
ER -