PDGFRα monoclonal antibody: Assessment of embryo-fetal toxicity and time-dependent placental transfer of a murine surrogate antibody of olaratumab in mice

2018 ◽  
Vol 110 (18) ◽  
pp. 1358-1371 ◽  
Author(s):  
Debra Luffer-Atlas ◽  
Vijayapal R. Reddy ◽  
Kim G. Hilbish ◽  
Curtis E. Grace ◽  
William J Breslin
Keyword(s):  
Monoclonal Antibody ◽  
Placental Transfer ◽  
Time Dependent ◽  
Fetal Toxicity

Thrombocytopenia after abciximab use results from different mechanisms

2010 ◽  
Vol 103 (03) ◽  
pp. 651-661 ◽  
Author(s):  
Gisèle Clofent-Sanchez ◽  
Pierre Coste ◽  
Paquita Nurden ◽  
Sophie Lajus ◽  
Catherine Jais ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Monoclonal Antibody ◽  
Flow Cytometry ◽  
Platelet Count ◽  
Time Dependent ◽  
Sensitive Test ◽  
Direct Elisa ◽  
Drug Dependent ◽  
Artery Disease ◽  
Antibody Specificities

SummaryOur study concerns thrombocytopenia in patients with acute ischaemic coronary artery disease receiving antiplatelet drugs to the αIIbβ3 inte-grin (GPIIb/IIIa). We have screened for drug-dependent antibodies (DDAB) in 18 patients who suffered a fall of > 50% in platelet count (9 patients had a nadir of <50,000 platelets/μl) after receiving abciximab and related results to clinical outcome. Serum or plasma was screened for DDAB using (i) a direct ELISA against purified αIIbβ3, αIIbβ3-abciximab complexes or abciximab alone, (ii) control platelets and flow cytometry and (iii) monoclonal antibody immobilisation of platelet antigens. DDAB were found for 11 patients, with αIIbβ3 ELISA the most sensitive test. Progressive platelet consumption linked with haemoglobin loss and/or use of intra-aortic balloon pumping, another potential cause of a fall in platelet count, was also evaluated. DDAB were identified that recognised αIIbβ3 associated with abciximab and/ or abciximab alone. Screening of both progressive and delayed thrombocytopenia (appearing after 5 to 11 days) suggested that antibodies against abciximab preceded those recognising neo-epitopes on αIIbβ3, with a time-dependent broadening of antibody specificities. Higher titres were seen after second abciximab use. Five antibodies were platelet-activating. In conclusion, the mechanisms responsible for this complication of anti-αIIbβ3 therapy are multiple and often associated with a complex immune response.

scholarly journals Evaluation of transplacental transfer of mRNA vaccine products and functional antibodies during pregnancy and early infancy

2021 ◽  
Author(s):  
Mary Prahl ◽  
Yarden Golan ◽  
Arianna G. Cassidy ◽  
Yusuke Matsui ◽  
Lin Li ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Placental Transfer ◽  
Maternal Blood ◽  
Early Infancy ◽  
Time Dependent ◽  
Transplacental Transfer ◽  
Protective Antibodies ◽  
Functional Antibodies ◽  
Epitope Binding ◽  
Efficient Transfer

Studies are needed to evaluate the safety and effectiveness of mRNA SARS-CoV-2 vaccination during pregnancy, and the levels of protection provided to their newborns through placental transfer of antibodies. We evaluated the transplacental transfer of mRNA vaccine products and functional anti-SARS-CoV-2 antibodies during pregnancy and early infancy in a cohort of 20 individuals vaccinated during pregnancy. We found no evidence of mRNA vaccine products in maternal blood, placenta tissue, or cord blood at delivery. However, we found time-dependent efficient transfer of IgG and neutralizing antibodies to the neonate that persisted during early infancy. Additionally, using phage immunoprecipitation sequencing, we found a vaccine-specific signature of SARS-CoV-2 Spike protein epitope binding that is transplacentally transferred during pregnancy. In conclusion, products of mRNA vaccines are not transferred to the fetus during pregnancy, however timing of vaccination during pregnancy is critical to ensure transplacental transfer of protective antibodies during early infancy.

scholarly journals The Removal of HBV in Plasma by Extracorporeal Immunoadsorption from Plasma: A Potential Therapy of Hepatitis B Patients

2018 ◽  
Vol 2018 ◽  
pp. 1-7
Author(s):  
Zhenwei Han ◽  
Xuan Lu ◽  
Yiping Tang ◽  
Yuanyuan Yang ◽  
Qiuchen Liu ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Scanning Electron Microscopy ◽  
Monoclonal Antibody ◽  
Time Dependent ◽  
The Novel ◽  
Plasma Samples ◽  
Novel Therapy ◽  
Real Time Quantitative Pcr ◽  
Therapy Option ◽  
Scanning Electron

Objective. To establish a novel HBV specific immunoadsorbent for the removing of HBV particles.Methods. The anti-HBsAg monoclonal antibody was immobilized on sepharose beads to produce a sepharose anti-HBs column. Then the immunoadsorbent was evaluated and characterized by scanning electron microscopy. In addition, time-dependent effects of the eradication capacity of anti-HBsAg functionalized sepharose beads against HBV were investigated.Results. Proposed immunoadsorbents exhibited a favorable biocompatibility as well as specificity. With the optimized recycle time, the decontamination performance of HBV particles and quantity of HBsAg were assessed either by real-time quantitative PCR or ELISA, which showed that the immunoadsorbent could remove approximately 90% of the HBV and 90% of the HBsAg from human plasma samples.Conclusions. All these results indicated that the novel immunoadsorbent could effectively remove HBV particles and likely serve as a novel therapy option or at least supplementary for the treatment regimen of HBV.

scholarly journals High Risk of Embryo-Fetal Toxicity: Placental Transfer of T-2 Toxin and Its Major Metabolite HT-2 Toxin in BeWo Cells

2013 ◽  
Vol 137 (1) ◽  
pp. 168-178 ◽  
Author(s):  
Xu Wang ◽  
Weiwei Wang ◽  
Guyue Cheng ◽  
Lingli Huang ◽  
Dongmei Chen ◽  
...  
Keyword(s):  
High Risk ◽  
Placental Transfer ◽  
Major Metabolite ◽  
Bewo Cells ◽  
Fetal Toxicity

TGF-β1 monoclonal antibody: Assessment of embryo-fetal toxicity in rats and rabbits

2016 ◽  
Vol 107 (4-5) ◽  
pp. 174-184 ◽  
Author(s):  
Kim G. Hilbish ◽  
Jennifer A. Martin ◽  
Anja J. Stauber ◽  
Tammye L. Edwards ◽  
William J. Breslin
Keyword(s):  
Monoclonal Antibody ◽  
Fetal Toxicity ◽  
Tgf Β1

scholarly journals Efficient Mother-to-Child Transfer of Antiretroviral Immunity in the Context of Preclinical Monoclonal Antibody-Based Immunotherapy

2006 ◽  
Vol 80 (20) ◽  
pp. 10191-10200 ◽  
Author(s):  
Laurent Gros ◽  
Mireia Pelegrin ◽  
Marc Plays ◽  
Marc Piechaczyk
Keyword(s):  
Monoclonal Antibody ◽  
Viral Load ◽  
Immune Responses ◽  
Placental Transfer ◽  
Humoral Response ◽  
Antiviral Effect ◽  
Late Gestation ◽  
Adult Age ◽  
Therapeutic Consequences ◽  
Neutralizing Monoclonal Antibody

ABSTRACT When mice under the age of 5 to 6 days are infected, the FrCasE retrovirus induces a neurodegenerative disease leading to death within 1 to 2 months. We have recently reported that transient treatment with a neutralizing monoclonal antibody (MAb) shortly after infection, in addition to an expected immediate decrease in the viral load, also favors the development of a strong protective immune response that persists long after the MAb has been cleared. This observation may have important therapeutic consequences, as it suggests that MAbs might be used, not only as direct neutralizing agents, but also as immunomodulatory agents enabling patients to mount their own antiviral immune responses. We have investigated whether immunoglobulins from mothers who displayed a strong anti-FrCasE humoral response induced upon MAb treatment could affect both viremia and the immune systems of FrCasE-infected pups till adult age upon placental and/or breastfeeding transfer. The strongest effects, i.e., reduction in the viral load and induction of protective humoral antiviral responses, were observed upon breastfeeding alone and breastfeeding plus placental immunity transfer. However, placental transfer of anti-FrCasE antibodies was sufficient to both protect neonatally infected animals and help them initiate a neutralizing anti-FrCasE response. Also, administration of a neutralizing MAb to naive mothers during late gestation and breastfeeding could generate similar effects. Taken together, our data support the concept that passive immunotherapies during late gestation and/or breastfeeding might help retrovirally infected neonates prime their own protective immune responses, in addition to exerting an immediate antiviral effect.

scholarly journals Adhesive protein expression on thrombin-stimulated platelets: time- dependent modulation of anti-fibrinogen, -fibronectin, and -von Willebrand factor antibody binding

Blood ◽  
1992 ◽  
Vol 79 (4) ◽  
pp. 948-953 ◽  
Author(s):  
EI Peerschke
Keyword(s):  
Monoclonal Antibody ◽  
Von Willebrand Factor ◽  
Polyclonal Antibody ◽  
Time Course ◽  
Surface Membrane ◽  
Membrane Receptors ◽  
Time Dependent ◽  
Adhesive Proteins ◽  
Von Willebrand ◽  
Willebrand Factor

Platelets contain a pool of endogenous adhesive proteins that can be released and may bind to surface membrane receptors under appropriate conditions. Because the binding of exogenous fibrinogen to platelets was shown previously to be accompanied by a time-dependent decrease in fibrinogen accessibility to antibody and enzymes, studies were performed to evaluate changes in the expression of endogenous fibrinogen released from thrombin-stimulated platelets using monospecific polyclonal and monoclonal antibody F(ab')2 fragments. Parallel studies were performed to compare the expression of released fibronectin and von Willebrand factor (vWF). Binding of polyclonal antibody F(ab')2 fragments directed against individual adhesive proteins was inhibited by EDTA or the 10E5 monoclonal antibody, suggesting that fibrinogen, fibronectin, and vWF expression was mediated, in large part, by divalent cation-dependent interactions with the glycoprotein IIb-IIIa complex. Interestingly, when polyclonal antibody F(ab')2 fragments were added to platelet suspensions at discrete times after thrombin stimulation, antifibrinogen F(ab')2 binding decreased by 72% +/- 15% (mean +/- SD, n = 22) over a 60-minute time course, whereas antifibronectin and anti-vWF antibody F(ab')2 fragment binding changed minimally (6% +/- 23%, n = 22 and 3% +/- 26%, n = 14, respectively). Similar observations were made with monoclonal antibodies. Parallel experiments using 125I-labeled fibrinogen as a marker indicated that the observed decrease in antifibrinogen F(ab')2 binding was not accompanied by fibrinogen dissociation. Moreover, antibody accessibility to platelet-bound fibrinogen could be restored after Triton X-100 platelet lysis. The data suggest that fibrinogen, fibronectin, and vWF are not coordinately expressed on thrombin- stimulated platelets. Rather, fibrinogen expression appears transient compared with the expression of fibronectin and vWF. The ability of platelets to secrete and organize adhesive proteins on their surface is likely to have important implications for hemostasis and thrombosis.

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