scholarly journals Immunotherapy Targeting Inhibitory Fcγ Receptor IIB (CD32b) in the Mouse Is Limited by Monoclonal Antibody Consumption and Receptor Internalization

2013 ◽  
Vol 191 (8) ◽  
pp. 4130-4140 ◽  
Author(s):  
Emily L. Williams ◽  
Alison L. Tutt ◽  
Stephen A. Beers ◽  
Ruth R. French ◽  
Claude H. T. Chan ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Receptor Internalization ◽  
Fcγ Receptor

A Monoclonal Antibody Inhibiting Human Placental Fcγ-Receptor Activity

1984 ◽  
Vol 75 (3) ◽  
pp. 227-229 ◽  
Author(s):  
Roald Matre ◽  
Lars R. Haaheim ◽  
Olav Tönder
Keyword(s):  
Monoclonal Antibody ◽  
Receptor Activity ◽  
Fcγ Receptor

Purification of a functional 40 kD human placental Fcγ-receptor using a monoclonal antibody

Apmis ◽  
1989 ◽  
Vol 97 (7-12) ◽  
pp. 733-737 ◽  
Author(s):  
ROALD MATRE ◽  
EINAR K. KRISTOFFERSEN ◽  
ELLING ULVESTAD ◽  
CHRISTIAN A. VEDELER
Keyword(s):  
Monoclonal Antibody ◽  
Fcγ Receptor

scholarly journals Fc-Glycosylation Influences Fcγ Receptor Binding and Cell-Mediated Anti-HIV Activity of Monoclonal Antibody 2G12

2010 ◽  
Vol 185 (11) ◽  
pp. 6876-6882 ◽  
Author(s):  
Donald N. Forthal ◽  
Johannes S. Gach ◽  
Gary Landucci ◽  
Jakub Jez ◽  
Richard Strasser ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Receptor Binding ◽  
Fcγ Receptor ◽  
Anti Hiv ◽  
Antibody 2G12

Murine Fcγ receptor proteins: identification of a previously unrecognized molecule with a monoclonal antibody (12-15)

1988 ◽  
Vol 18 (5) ◽  
pp. 677-683 ◽  
Author(s):  
Peter Altevogt ◽  
Gitte Heckl-Oestreichep ◽  
Elke Lang ◽  
Ulrike Kohl ◽  
Hartmut Kratzin ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Fcγ Receptor ◽  
Receptor Proteins

scholarly journals Fcγ Receptor Activation by Human Monoclonal Antibody Aggregates

2020 ◽  
Vol 109 (1) ◽  
pp. 576-583 ◽  
Author(s):  
Minoru Tada ◽  
Michihiko Aoyama ◽  
Akiko Ishii-Watabe
Keyword(s):  
Monoclonal Antibody ◽  
Human Monoclonal Antibody ◽  
Receptor Activation ◽  
Fcγ Receptor

Phase I dose escalation study of the anti-IGF-1R monoclonal antibody CP-751,871 in patients with refractory solid tumors

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 3586-3586 ◽  
Author(s):  
P. Haluska ◽  
H. Shaw ◽  
G. N. Batzel ◽  
L. R. Molife ◽  
A. A. Adjei ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Phase I ◽  
Solid Tumors ◽  
Dose Escalation ◽  
Receptor Internalization ◽  
Pharmacokinetic Analysis ◽  
Adrenocortical Cancer ◽  
Dose Escalation Study ◽  
Multiple Tumor ◽  
Grade 3

3586 Background: The insulin-like growth factor 1 receptor (IGF-IR), a tyrosine kinase, and its ligands (IGF-I & -2) are upregulated in many human tumors (e.g., breast, prostate, colon and non-small cell lung cancer) and enhance proliferative and prosurvival signaling. Inhibition of IGF-IR activation in tumor models suppresses tumor growth and increases tumor sensitivity to chemotherapy, supporting the development of agents targeting IGF-IR. CP-751,871 is a potent, highly specific, fully humanized, monoclonal antibody that inhibits IGF-IR autophosphorylation and induces receptor internalization. Methods: A Phase I dose escalation study was initiated to define the safety and tolerability, and to characterize the pharmacokinetic properties of CP-751,871 in patients with advanced solid tumors refractory to standard therapies. Results: Following informed consent and screening, a total of 24 patients with refractory solid tumors (e.g. colorectal, NSCLC, sarcoma and prostate cancer; 1–6 previous regimens) were enrolled. Patients received 3 to 20 mg/kg of CP-751,871 by IV infusion on Day 1 of 3-week cycles in four dose-escalation cohorts of 3 patients. No dose limiting toxicities were identified and the maximum feasible dose (MFD) cohort of 20 mg/kg was extended with 12 additional patients. No higher than grade 3 CTCAE v3.0 toxicities, attributed to study drug, have been so far reported. Grade 3 toxicities, all reported in patients dosed with 20 mg/kg of CP-751,871, are increased GGT (4%) and fatigue (4%). Grade 2 toxicities include: anorexia (7%), diarrhea (7%), increased GGT (4%), hyperglycemia (4%), fatigue (4%), increased urinary frequency (4%), nausea (4%), increased ALT (4%) and increased AST (4%). Pharmacokinetic analysis is currently ongoing. No objective responses were observed. At the MFD, patients received a median of 4 cycles (1–16). Three patients were stable for > 6 months and one patient, currently at cycle 16, remains on study. An additional cohort of 12 adrenocortical cancer patients is under evaluation. Conclusions: These data indicate that CP-751,871 is safe and well tolerated. Due to its good safety profile, CP-751,871 may constitute a suitable targeted agent to use in combination with approved therapies in multiple tumor types. No significant financial relationships to disclose.

scholarly journals The Therapeutic CD38 Monoclonal Antibody Daratumumab Induces Programmed Cell Death via Fcγ Receptor–Mediated Cross-Linking

2016 ◽  
Vol 197 (3) ◽  
pp. 807-813 ◽  
Author(s):  
Marije B. Overdijk ◽  
J. H. Marco Jansen ◽  
Maaike Nederend ◽  
Jeroen J. Lammerts van Bueren ◽  
Richard W. J. Groen ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Cross Linking ◽  
Fcγ Receptor

CD44 Antibody Mediated Amelioration of Murine ITP: Evidence for a Similar Strain Dependent FcγRIIB Requirement As Compared to Ivig

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1084-1084
Author(s):  
Andrew R. Crow ◽  
Alan H Lazarus
Keyword(s):  
Monoclonal Antibody ◽  
Conflicts Of Interest ◽  
Fcγ Receptor ◽  
Fcγ Receptors ◽  
Background Strain ◽  
Cast Doubt ◽  
Antibody Function ◽  
Strain Dependent ◽  
Deficient Mice ◽  
Cd44 Antibody

Abstract Abstract 1084 We have previously demonstrated that monoclonal antibodies to the CD44 antigen can ameliorate murine ITP as successfully as IVIg. We have also shown that, similar to IVIg, these antibodies do not require expression of the neonatal Fcγ receptor FcRn. Unlike IVIg, however, CD44 antibodies do not require the Fc portion to function in the murine ITP model. A lack of requirement for the Fc region of CD44 antibodies would indicate that Fcγ receptors should not be necessary for antibody function, but CD44 antibodies do not ameliorate ITP in FcγRIIB deficient mice (B6;129S-Fcgr2btm1Ttk/J). Recent data from some groups have suggested that IVIg can in fact ameliorate murine ITP in the absence of FcγRIIB, depending on the background strain of the mouse. These data cast doubt on the simplistic view that IVIg ameliorates murine ITP by upregulating macrophage FcγRIIB expression. The requirement for the expression of the inhibitory IgG receptor FcγRIIB has been a prominent theory as to how IVIg ameliorates ITP. Similar to IVIg, the CD44 antibody KM114 does not function in B6;129S-Fcgr2btm1Ttk/J FcγRIIB deficient mice. Another IVIg product which has ameliorative effects similar to IVIg but appears to function via a different mechanism is anti-D. We have previously shown that IVIg and a monoclonal antibody with “anti-D like” activity, TER-119, can successfully ameliorate thrombocytopenia in a murine model of ITP. In contrast to KM114 and IVIg, TER-119 is fully functional in B6;129S-Fcgr2btm1Ttk/J mice. To further characterize the therapeutic CD44 antibody KM114, we have analysed KM114 function in FcγRIIB deficient mice on 3 different backgrounds. Specifically, mice were pretreated with nothing, 50 ug KM114, 50 mg IVIg, or 50 ug TER-119 thirty min prior to administration of the anti-platelet antibody MWReg30. Here, we have confirmed that TER-119, but not KM114 or IVIg, successfully ameliorates murine ITP in B6;129S-Fcgr2btm1Ttk/J mice. These mice are not fully congenic, and have been reported to be approximately a 50:50 mix of B6 and 129S4 (Leontyev, et. al Blood. 31;119(22):5261-4). To investigate whether or not KM114 required the presence of FcγRIIB in mice from different backgrounds, we next employed B6.129S4-Fcgr2btm1TtK N12 FcγRIIB deficient mice, which, unlike B6;129S-Fcgr2btm1Ttk/J mice, are congenic on the B6 background. KM114 and IVIg were both effective in treating thrombocytopenia in these mice. TER-119 was also effective, as expected. To further explore these findings, we next employed FcγRIIB deficient mice which are congenic on the BALB/C background, C.129S4(B6)-Fcgr2btm1TtK/cAnNTac N12 mice. Again, we found that KM114, IVIg and TER-119 were all effective in treating thrombocytopenia in these mice. As KM114 functions in congenic B6.129S4-Fcgr2btm1TtK N12 and C.129S4(B6)-Fcgr2btm1TtK/cAnNTac N12 mice, but not in mixed background B6;129S-Fcgr2btm1Ttk/J mice, these data suggest that rather than FcγRIIB expression being necessary, it may be the mouse background genes that affect KM114's ability to function. Further experiments using mice of different genetic backgrounds may assist in understanding these findings. Disclosures: No relevant conflicts of interest to declare.

Production of a Monoclonal Antibody Directed against the High-Affinity Nerve Growth Factor Receptor

1999 ◽  
Vol 14 (2) ◽  
pp. 68-72 ◽  
Author(s):  
E. Tagliabue ◽  
C. Ghirelli ◽  
L. Lombardi ◽  
F. Castiglioni ◽  
L. Asnaghi ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Neuroblastoma Cell ◽  
Growth Factor Receptor ◽  
Nerve Growth Factor Receptor ◽  
Receptor Internalization ◽  
Growth Modulation ◽  
Nerve Growth ◽  
High Affinity

The high-affinity nerve growth factor receptor corresponds to the tyrosine protein kinase encoded by the proto-oncogene trkA. Different findings suggest that nerve growth factor (NGF) can be operative in the growth modulation of tumor cell lines possessing high-affinity binding sites for this molecule. Using as immunizing material the SKNBE neuroblastoma cell line transfected with proto-trkA we produced a monoclonal antibody (MAb) able to recognize the high-affinity nerve growth factor receptor. The selected MAb, designated MGR12, is directed against an epitope present on the extracellular domain of the receptor since it showed reactivity on living trkA-expressing cells and was able to immunoprecipitate the proto-trkA molecule. The MGR12 MAb is directed against a non-functional epitope since it neither inhibited NGF binding nor induced receptor internalization. This new reagent appears to be an appropriate tool for analyzing the expression of high-affinity nerve growth factor receptor in tumors of different origin and for elucidating its involvement in tumor progression.

scholarly journals Monoclonal antibody-induced ErbB3 receptor internalization and degradation inhibits growth and migration of human melanoma cells

Cell Cycle ◽  
2012 ◽  
Vol 11 (7) ◽  
pp. 1455-1467 ◽  
Author(s):  
Francesca Belleudi ◽  
Emanuele Marra ◽  
Francesca Mazzetta ◽  
Luigi Fattore ◽  
Maria Rosaria Giovagnoli ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Melanoma Cells ◽  
Human Melanoma ◽  
Receptor Internalization ◽  
Human Melanoma Cells ◽  
And Migration
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