Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 7509-7514 |
| Number of pages | 6 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 94 |
| Issue number | 14 |
| DOIs | |
| State | Published - Jul 8 1997 |
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ASJC Scopus subject areas
- Genetics
- General
Cite this
Homodimerization of tumor-reactive monoclonal antibodies markedly increases their ability to induce growth arrest or apoptosis of tumor cells. / Ghetie, Maria Ana; Podar, Erika M.; Ilgen, Amy; Gordon, Brian E.; Uhr, Jonathan W.; Vitetta, Ellen S.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 94, No. 14, 08.07.1997, p. 7509-7514.Research output: Contribution to journal › Article
}
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.
UR - http://www.scopus.com/inward/record.url?scp=0030806221&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0030806221&partnerID=8YFLogxK
U2 - 10.1073/pnas.94.14.7509
DO - 10.1073/pnas.94.14.7509
M3 - Article
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
SN - 0027-8424
IS - 14
ER -