Journal: Clinical cancer research : an official journal of the American Association for Cancer Research

Article Title: Retooling a Blood-based Biomarker: Phase I Assessment of the High-Affinity CA19-9 Antibody HuMab-5B1 for Immuno-PET Imaging of Pancreatic Cancer

doi: 10.1158/1078-0432.CCR-18-3667

Figure Lengend Snippet: A, There is a reduction in liver uptake of radioactivity with increasing antibody mass (error bars show one standard deviation). B, Maximum-intensity projection image demonstrates the effect in a patient injected with 3 mg antibody (left) and a (different) patient injected with 47 mg HuMab 5B1 antibody 2 h before injection of 3 mg radiolabeled HuMab 5B (right). C, Fused PET/CT, PET, and contrast-enhanced CT of PDAC liver metastases in a patient who received 47 mg of HuMab 5B1 before injection of the radiolabeled antibody. Small liver metastases measuring less than 5 mm (red arrows) are visualized with high contrast. SUVs values were 101.4, 70.7, and 53.4 g/ml, respectively. Arrowhead indicates splenic infarct.

Article Snippet: The fully human HuMab-5B1 antibody was manufactured for MabVax Therapeutics Holdings, Inc. (San Diego, CA) by Patheon Biologics (Groningen, Netherlands) under current good manufacturing practice (cGMP) guidelines and supplied in sterile vials to MSK.

Techniques: Radioactivity, Standard Deviation, Injection, Positron Emission Tomography-Computed Tomography

Journal: Blood

Article Title: Recombinant von Willebrand factor prophylaxis in patients with severe von Willebrand disease: phase 3 study results

doi: 10.1182/blood.2021014810

Figure Lengend Snippet: Patient disposition. *Primary reason: platelet count <100 000/mL at screening (n = 1), scheduled for surgical intervention (n = 1), history or presence of a VWF inhibitor at screening (n = 1), patient not willing or able to comply with protocol requirements (n = 2), VWD inclusion criteria not met (n = 1). †Patients who were treated on-demand with any VWF during the 12-month period before enrolling in this study. ‡Patients who were treated prophylactically with a pdVWF for ≥12 months before enrolling in this study. §Nonserious headache (moderate intensity), which was considered by the investigator to be possibly related to rVWF and began during an rVWF infusion. ‖One patient in each group withdrew consent for reasons unrelated to efficacy/bleeding, and 1 patient in the prior on-demand group was lost to follow-up. ¶Scheduled for extended treatment with hydrocortisone >10 mg per day (not permitted during the study). **Required treatment with high corticosteroid doses for rheumatoid arthritis (not permitted during the study). ††All patients who were enrolled and received any amount of rVWF. ‡‡All patients who received rVWF prophylaxis. §§All patients who received ≥1 rVWF infusion and provided ≥1 quantifiable PK/PD postdose measurement. FAS, full analysis set; PKFAS, pharmacokinetic full analysis set; SAS, safety analysis set.

Article Snippet: VWF:RCo mean half-life (t 1/2 ) for rVWF (17.2 hours) at the initial assessment for the prior on-demand group was comparable with previously reported data (between 17.8 and 22.6 hours), and is longer than the t 1/2 values reported for the pdVWF products Humate P (antihemophilic factor/VWF complex [human]; CSL Behring GmbH, Marburg, Germany: mean, 12.8 hours ) and Voncento (human coagulation FVIII/human VWF complex; CSL Behring GmbH, Marburg, Germany: mean, 13.7 hours ).

Techniques:

Journal: Cellular immunology

Article Title: Suppression of anti-drug antibody formation against coagulation factor VIII by oral delivery of anti-CD3 monoclonal antibody in hemophilia A mice

doi: 10.1016/j.cellimm.2023.104675

Figure Lengend Snippet: ( A ) Timeline for pre-α-CD3 oral administration. HA mice received oral gavage with 0.5 or 5 μg/ mouse of either α-CD3 full length (FL) or F(ab’) 2 for 5 consecutive days. 5 days following α-CD3 administration, mice received 5 weekly i.v. injections of 1.5 IU BDD-FVIII. Mice injected only with BDD-FVIII were used as control. Functional inhibitors were quantified by ( B ) Bethesda and ( C ) α-FVIII IgG1 ELISA. (D) Timeline for concurrent α-CD3 oral administration. Mice received oral gavage with 0.5 or 5 μg of either α-CD3 full length or F(ab’) 2 for 5 days, as above. On day 3, concurrent with oral α-CD3 treatment, mice received i.v. injection of 1.5 IU BDD-FVIII, which was then continued weekly for 5 weeks. Functional inhibitors were quantified by ( E ) Bethesda and ( F ) α-FVIII IgG1 ELISA. The frequency of animals in each group that develop ADAs are indicated in B and E . Data represent 2 ( Fig1C and D ) and 3 ( Fig1E and F ) independent experiments (n = 8–30). Data are represented as average ± SEM. Statistically significant differences as calculated by one-way ANOVA are indicated, where a p value <0.05 is considered statistically significant and is indicated as follows: *p < 0.05, **p < 0.01, ***p < 0.001, and ****p < 0.0001.

Article Snippet: Five days after the last α-CD3 administration, mice received weekly i.v. infusions of 1.5 IU BBD-human FVIII (Xyntha; Pfizer, New York, NY) for 5 weeks ( Figure 1A ).

Techniques: Injection, Control, Functional Assay, Enzyme-linked Immunosorbent Assay

Journal: Cellular immunology

Article Title: Suppression of anti-drug antibody formation against coagulation factor VIII by oral delivery of anti-CD3 monoclonal antibody in hemophilia A mice

doi: 10.1016/j.cellimm.2023.104675

Figure Lengend Snippet: ( A ) Timeline. HA mice received 5 consecutive daily injections of 0.5 or 5 μg of either α-CD3 full length or F(ab’) 2 , concurrent with i.v. injection of 1.5 IU BDD-FVIII on day 3, which was then continued weekly for 5 weeks. An additional group received only BDD-FVIII injections. Spleens and MLN were processed at weeks 1, 2 and 5 for quantifying total CD3 + and CD4 + T cell numbers. ( B ) CD3 + and CD4 + T cell numbers/ million lymphocytes from spleens of mice treated with either 0.5μg or 5μg of oral α-CD3 F(ab’) 2 at week 1 . CD3 + and CD4 + T cell numbers from naïve mice are used as control. ( C ) CD3 + and CD4 + T cell numbers/ million lymphocytes from MLN of mice treated with either 0.5μg or 5μg of oral α-CD3 F(ab’) 2 at week 1 . ( D ) CD3 + T cell and CD4 + T cell numbers/ million lymphocytes from spleens of mice treated with 0.5μg of oral α-CD3 F(ab’) 2 at week 2 . ( E ) CD4 + T cell numbers/ million lymphocytes from MLN of mice treated with 0.5μg of oral α-CD3 F(ab’) 2 at week 2 . ( F ) CD3 + T cell and CD4 + T cell numbers/ million lymphocytes from spleens of mice treated with either 0.5μg or 5μg of full length (FL) or F(ab’) 2 oral α-CD3 at week 5 . Data are average ± SEM of at least 4 mice per group and are a single representative of 1-3 independent experiments. Statistical differences as calculated by one-way ANOVA are indicated where applicable, where a p value <0.05 is considered statistically significant and indicated as follows: *p < 0.05, **p < 0.01, ***p < 0.001, and ****p < 0.0001.

Article Snippet: Five days after the last α-CD3 administration, mice received weekly i.v. infusions of 1.5 IU BBD-human FVIII (Xyntha; Pfizer, New York, NY) for 5 weeks ( Figure 1A ).

Techniques: Injection, Control

Journal: Cellular immunology

Article Title: Suppression of anti-drug antibody formation against coagulation factor VIII by oral delivery of anti-CD3 monoclonal antibody in hemophilia A mice

doi: 10.1016/j.cellimm.2023.104675

Figure Lengend Snippet: ( A ) Timeline. HA mice received 5 consecutive daily injections of 0.5 μg or 5 μg α-CD3 F(ab’) 2 , concurrent with i.v. injection of 1.5 IU BDD-FVIII on day 3, which was then continued weekly for 5 weeks. An additional group received only BDD-FVIII injections. Spleens and MLN were processed at weeks 1 and 2 for quantifying total FoxP3 + LAP − , FoxP3 + LAP + and FoxP3 − LAP + cell numbers. ( B ) FoxP3 + LAP − , FoxP3 + LAP + and FoxP3 − LAP + numbers/ million lymphocytes from spleens of mice treated with either 0.5μg or 5μg of oral α-CD3 F(ab’) 2 at week 1 . Cell numbers from naïve mice are used as control. ( C ) FoxP3 + LAP − , FoxP3 + LAP + and FoxP3 − LAP + numbers/ million lymphocytes from MLN of mice treated with either 0.5μg or 5μg of oral α-CD3 F(ab’) 2 at week 1 . ( D ) FoxP3 + LAP − , FoxP3 + LAP + and FoxP3 − LAP + numbers/ million lymphocytes from spleens of mice treated with 0.5μg of oral α-CD3 F(ab’) 2 at week 2 . ( E ) FoxP3 + LAP − , FoxP3 + LAP + and FoxP3 − LAP + numbers/ million lymphocytes from MLN of mice treated with 0.5μg of oral α-CD3 F(ab’) 2 at week 2 . Data are a single representative of 1-3 independent experiments with at least n=4/group. Statistical differences as calculated by one-way ANOVA are indicated where applicable, where a p value <0.05 is considered statistically significant and indicated as follows: *p < 0.05, **p < 0.01, ***p < 0.001, and ****p < 0.0001.

Article Snippet: Five days after the last α-CD3 administration, mice received weekly i.v. infusions of 1.5 IU BBD-human FVIII (Xyntha; Pfizer, New York, NY) for 5 weeks ( Figure 1A ).

Techniques: Injection, Control

Journal: Cellular immunology

Article Title: Suppression of anti-drug antibody formation against coagulation factor VIII by oral delivery of anti-CD3 monoclonal antibody in hemophilia A mice

doi: 10.1016/j.cellimm.2023.104675

Figure Lengend Snippet: ( A ) Timeline. HA mice received 5 consecutive daily injections of 0.5 or 5 μg of either α-CD3 full length (FL) or F(ab’) 2 , concurrent with i.v. injection of 1.5 IU BDD-FVIII on day 3, which was then continued weekly for 5 weeks. Control mice received only BDD-FVIII injections. Spleens were processed at week 5 for quantifying total FoxP3 + LAP − , FoxP3 + LAP + and FoxP3 − LAP + cell numbers. (B) Representative density plots displaying gating strategies for FoxP3 + LAP − , FoxP3 + LAP + , FoxP3 − LAP + Treg subsets and FoxP3 − LAP − CD4 + T conv cells. Frequencies of (C) FoxP3 + LAP − , (D) FoxP3 + LAP + , (E) FoxP3 − LAP + Treg, and (F) FoxP3 − LAP − T conv cells quantified as percent CD4 + T cells. Data are a single representative of at least 3 independent experiments with at least n=4/group. Statistical differences as calculated by one-way ANOVA are indicated where applicable, where a p value <0.05 is considered statistically significant and indicated as follows: *p < 0.05, **p < 0.01, ***p < 0.001, and ****p < 0.0001.

Article Snippet: Five days after the last α-CD3 administration, mice received weekly i.v. infusions of 1.5 IU BBD-human FVIII (Xyntha; Pfizer, New York, NY) for 5 weeks ( Figure 1A ).

Techniques: Injection, Control

Journal: Cellular immunology

Article Title: Suppression of anti-drug antibody formation against coagulation factor VIII by oral delivery of anti-CD3 monoclonal antibody in hemophilia A mice

doi: 10.1016/j.cellimm.2023.104675

Figure Lengend Snippet: HA mice received 5 consecutive daily injections of 0.5 α-CD3 F(ab’) 2 , concurrent with i.v. injection of 1.5 IU BDD-FVIII on day 3, which was then continued weekly for 5 weeks. Control mice received only BDD-FVIII injections. At week 5, spleens were phenotyped for activation and co-inhibitory receptor expression. (A) Surface expression of CD69, CTLA-4, PD1, and TIGIT in Foxp3 + LAP − , Foxp3 + LAP + and Foxp3 − LAP + cells as measured by median fluorescence intensity (MFI). (B) Percent of IL-10 expressing cells within Foxp3 + LAP − , Foxp3 + LAP + and Foxp3 − LAP + populations in 0.5 μg oral α-CD3 F(ab’) 2 treated mice as compared to control animals that received only BDD-FVIII injections. Data are average ± SEM of at least 3 mice per group and are the best representative of three or more independent experiments. Statistical differences as calculated by one-way ANOVA are indicated where applicable, where a p value <0.05 is considered statistically significant and is indicated as follows: *p < 0.05, **p < 0.01, ***p < 0.001, and ****p < 0.0001.

Article Snippet: Five days after the last α-CD3 administration, mice received weekly i.v. infusions of 1.5 IU BBD-human FVIII (Xyntha; Pfizer, New York, NY) for 5 weeks ( Figure 1A ).

Techniques: Injection, Control, Activation Assay, Expressing, Fluorescence

Journal: Cellular immunology

Article Title: Suppression of anti-drug antibody formation against coagulation factor VIII by oral delivery of anti-CD3 monoclonal antibody in hemophilia A mice

doi: 10.1016/j.cellimm.2023.104675

Figure Lengend Snippet: (A) Timeline of oral α-CD3 and/or FVIII lettuce administration and intravenous treatment with BDD-FVIII. Groups of HA mice (n=10-25) received a mixture of lettuce plant cells transgenic for HC and C2 domains of human FVIII (1.5 μg of FVIII antigen). Oral delivery of HC/C2 lettuce was carried out 2X/week for 2 months. 3 weeks into feeding, mice additionally received 5 μg oral α-CD3 FL or F(ab’) 2 antibody for 5 consecutive days as indicated. BDD-FVIII injections (1X/week for 5 weeks) commenced immediately after oral α-CD3 gavage. Control and single treatment groups received mock, only oral α-CD3, or only HC/C2 lettuce, followed by BDD-FVIII injections. (B) Functional inhibitor and (C) α-FVIII IgG1 ELISA titers for HA mice that received HC/C2 and/or 5 μg oral α-CD3 FL or F(ab’) 2 antibody. (D) Functional inhibitor and (E) α-FVIII IgG1 ELISA titers for HA mice that received HC/C2 and/or 0.5 μg oral α-CD3 F(ab’) 2 or FL antibody. The frequency of animals in each group that develop ADAs are indicated in B and D . Data are average ± SEM. Statistical differences as calculated by one-way ANOVA are indicated where applicable, where a p value <0.05 is considered statistically significant and indicated as follows: *p < 0.05, **p < 0.01, ***p < 0.001, and ****p < 0.0001.

Article Snippet: Five days after the last α-CD3 administration, mice received weekly i.v. infusions of 1.5 IU BBD-human FVIII (Xyntha; Pfizer, New York, NY) for 5 weeks ( Figure 1A ).

Techniques: Transgenic Assay, Control, Functional Assay, Enzyme-linked Immunosorbent Assay