M. Ghetie

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Her-2 (p185(erbB-2)) is a transmembrane tyrosine kinase receptor, which is encoded by the Her-2/neu proto-oncogene. Her-2 is overexpressed on 30% of highly malignant breast cancers. Monoclonal antibodies (MAbs) against Her-2 inhibit the growth of Her-2-overexpressing tumor cells and this occurs by a variety of mechanisms. One such MAb, Herceptin(More)
In this report, we extend our previous findings that IgG or F(ab')2 fragments of HD37 anti-CD19 antibody (Ab) in combination with the immunotoxin (IT), RFB4-anti-CD22-deglycosylated ricin A chain (dgA) (but neither reagent alone), prolonged the survival of SCID mice with disseminated human Daudi lymphoma (SCID/Daudi mice) to 1 year at which time they still(More)
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(More)
PURPOSE The purpose of this study was to prepare chimeric antihuman CD22 tetravalent monoclonal antibodies (MAbs) with high functional affinity, long persistence in the circulation, increased antitumor activity, and conserved effector function in vitro. EXPERIMENTAL DESIGN We investigated the association/dissociation rates of these tetravalent antibodies(More)
A human Burkitt lymphoma (Daudi) has been grown in the mutant mouse called C.B-17 SCID. Twenty-eight days after s.c. injection of Daudi cells, a palpable tumor grew only at the site of injection in all injected mice. In contrast, after intravenous (i.v.) or intraperitoneal (i.p.) injection, macroscopic, disseminated tumors developed. Following i.v.(More)
The antitumor activities of immunotoxins (ITs) constructed with deglycosylated ricin A chain (dgA) and either anti-CD19 (HD37) or anti-CD22 (RFB4) monoclonal antibodies were compared in SCID mice with disseminated human Daudi lymphoma (SCID/Daudi). As reported previously, after intravenous injection with Daudi cells, SCID mice develop disseminated lymphoma,(More)
In 1997, a chimeric anti-CD20 monoclonal antibody (mAb) (Rituxan) was approved for the treatment of low-grade/follicular B-cell lymphoma. Rituxan has a long half-life and low immunogenicity, and it mediates effector function. Rituxan induces apoptosis in some tumor cell lines in vitro. Previous studies with mAbs that react with neoplastic B cells have(More)
Ricin A chain-containing immunotoxins (IT-As) specific for the human B-cell antigen, CD22, were prepared from 4 monoclonal antibodies (MAbs) or their Fab' fragments: RFB4, HD6, UV22-I and UV22-2. The ITs were tested for their ability to kill cells from the Burkitt lymphoma line, Daudi, the pre-B-cell leukemia line, NALM-6, and the myeloma cell line, ARH-77.(More)
We have previously demonstrated that an anti-CD19 monoclonal antibody (MAb; HD37) inhibits the function of the P-glycoprotein (P-gp) pump in a multidrug-resistant (MDR) B-lymphoma cell line, Namalwa/MDR1, and that this effect is not due to the recognition of a cross-reactive epitope on P-gp. In this study, we have used the same cell line to define the(More)