Mathematical PKPD and safety model of bispecific TfR/BACE1 antibodies for the optimization of antibody uptake in brain

2016 ◽  
Vol 101 ◽  
pp. 53-61 ◽  
Author(s):  
Kapil Gadkar ◽  
Daniela Bumbaca Yadav ◽  
Joy Yu Zuchero ◽  
Jessica A. Couch ◽  
Jitendra Kanodia ◽  
...  
Keyword(s):  
1989 ◽  
Vol 44 (6) ◽  
pp. 1041-1047 ◽  
Author(s):  
R. D. Blumenthal ◽  
R. M. Sharkey ◽  
R. Kashi ◽  
A. M. Natale ◽  
D. M. Goldenberg

2010 ◽  
Vol 21 (12) ◽  
pp. 2078-2086 ◽  
Author(s):  
Najate Benhra ◽  
Françoise Vignaux ◽  
Aurore Dussert ◽  
François Schweisguth ◽  
Roland Le Borgne

Notch receptors mediate short-range signaling controlling many developmental decisions in metazoans. Activation of Notch requires the ubiquitin-dependent endocytosis of its ligand Delta. How ligand endocytosis in signal-sending cells regulates receptor activation in juxtaposed signal-receiving cells remains largely unknown. We show here that a pool of Delta localizes at the basolateral membrane of signal-sending sensory organ precursor cells in the dorsal thorax neuroepithelium of Drosophila and that Delta is endocytosed in a Neuralized-dependent manner from this basolateral membrane. This basolateral pool of Delta is segregated from Notch that accumulates apically. Using a compartimentalized antibody uptake assay, we show that murine Delta-like 1 is similarly internalized by mNeuralized2 from the basolateral membrane of polarized Madin-Darby canine kidney cells and that internalized ligands are transcytosed to the apical plasma membrane where mNotch1 accumulates. Thus, endocytosis of Delta by Neuralized relocalizes Delta from the basolateral to the apical membrane domain. We speculate that this Neuralized-dependent transcytosis regulates the signaling activity of Delta by relocalizing Delta from a membrane domain where it cannot interact with Notch to another membrane domain where it can bind and activate Notch.


PEDIATRICS ◽  
1974 ◽  
Vol 54 (6) ◽  
pp. 718-723
Author(s):  
Katherine Sprunt ◽  
Dorothea Vail ◽  
Russell S. Asnes

A rapid screening method for identification of clinic patients with pharyngitis who are carrying group A beta-hemolytic streptococci and for teaching residents the values and limitations of the culture-disk approach to identification has been reviewed as developed for a busy clinic and a busy hospital laboratory. Identification of positive cultures in less than 24 hours, using Taxos A disk and specific fluorescent antibody uptake, resulted in 12% apparent false-positive and 3.6% false-negative reports. However, when viewed in the light of the techniques used for verifying results, there were probably 3% false-positive and 3% false-negative reports. The screening method is considered acceptably reliable and practical as a laboratory tool and a resident teaching device.


1992 ◽  
Vol 65 (780) ◽  
pp. 1086-1092
Author(s):  
A. Jiménez-Heffernan ◽  
J. M. Latre ◽  
M. Concha ◽  
M. Torres ◽  
M. Martínez-Paredes ◽  
...  

1992 ◽  
Vol 7 (3) ◽  
pp. 198-202 ◽  
Author(s):  
S. Lastoria ◽  
C. Caracò ◽  
E. Vergara ◽  
L. Castelli ◽  
M. Salvatore

Localization of gastrointestinal tumors by means of labeled monoclonal antibodies is a new, sensitive and suitable technique currently used in several centers. Encouraging results have been documented with several monoclonal antibodies by different authors. This article reviews our experience with radioimmunoscintigraphy in 59 patients with colorectal cancer in follow-up, using 131I and 111In labeled B72.3, and in 16 patients with primary gastrointestinal tumors using 99mTc anti-CEA monoclonal antibody (type F023C5). The sensitivity of both B72.3 and anti-CEA was greater than 70% either for primary tumors and abdominal recurrences or distant metastases except hepatic ones. A significant gradient in antibody uptake was measured on surgical biopsies between tumors and normal tissues allowing a good in vivo contrast for gamma detection. We have defined the impact of some factors affecting in vivo tumor targeting. In fact, pharmacodynamics of MAbs, percentage of injected dose bound to tissues were measured, and in particular antigenic content in tumor nodules was quantified. Furthermore, the results of RIS were compared to those obtained by CT and other imaging modalities.


1989 ◽  
Vol 16 (3) ◽  
pp. 715-720 ◽  
Author(s):  
Jeffrey Y.C. Wong ◽  
Lawrence E. Williams ◽  
L. Robert Hill ◽  
Raymond J. Paxton ◽  
Barbara G. Beatty ◽  
...  

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