scholarly journals Dosimetric analysis of chimeric monoclonal antibody cMOv18 IgG in ovarian carcinoma patients after intraperitoneal and intravenous administration

1998 ◽  
Vol 25 (11) ◽  
pp. 1552-1561 ◽  
Author(s):  
W. C. A. M. Buijs ◽  
J. G. Tibben ◽  
O. C. Boerman ◽  
C. F. M. Molthoff ◽  
L. F. A. G. Massuger ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Ovarian Carcinoma ◽  
Intravenous Administration ◽  
Chimeric Monoclonal Antibody ◽  
Dosimetric Analysis

scholarly journals Targeting of renal cell carcinoma with iodine-131-labeled chimeric monoclonal antibody G250.

1997 ◽  
Vol 15 (4) ◽  
pp. 1529-1537 ◽  
Author(s):  
M G Steffens ◽  
O C Boerman ◽  
J C Oosterwijk-Wakka ◽  
G O Oosterhof ◽  
J A Witjes ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Monoclonal Antibody ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Enzyme Linked Immunosorbent Assay ◽  
Primary Tumors ◽  
Chimeric Monoclonal Antibody ◽  
Imaging Characteristics ◽  
Iodine 131 ◽  
Dosimetric Analysis

PURPOSE Pharmacokinetics, biodistribution, immunogenicity, and imaging characteristics of iodine 131 (131I)-labeled chimeric monoclonal antibody (mAb) G250 (cG250) were studied in patients with renal cell carcinoma (RCC) to determine the therapeutic potential of this antibody. PATIENTS AND METHODS Sixteen patients with RCC received a single intravenous (IV) infusion of 6 mCi 131I-labeled cG250. Five protein dose levels were investigated (2 to 50 mg). Planar scintigraphic images were acquired, and normal tissue biopsies and tumor samples were obtained of surgery (7 days postinjection). The immunogenicity of cG250 was investigated using a sandwich enzyme-linked immunosorbent assay (ELISA) and dosimetric analysis was performed. RESULTS In all patients with antigen-positive tumors (n = 13), the primary tumors and all known metastases were clearly visualized. Overall uptake, expressed as the percentage of the injected dose (%ID), in the primary tumors ranged from 2.4 to 9.0. Focally, 131I-cG250 uptake as high as 0.52% ID/g was observed. However, intratumoral uptake was highly heterogeneous. 131I-cG250 uptake in nontumorous tissues remained low. Dosimetric analysis showed that up to .48 Gy/mCi was guided to the primary tumors. Selected "hot areas" within these tumors received up to .72 Gy/mCi. A bone metastasis received .23 Gy/mCi and regional lymph node metastases received .20 Gy/mCi. Minimal human antichimeric antibody (HACA) levels were detected in two of 16 patients. CONCLUSION 131I-cG250 tumor uptake is among the highest reported in clinical studies with antitumor antibodies in solid tumors. Since tumor-sterilizing levels may be guided to the tumor when high doses 131I-cG250 are administered (> 100 mCi) and cG250 appears to be immunosilent, cG250 is a promising vehicle for radioimmunotherapy in RCC.

Escalating protein doses of chimeric monoclonal antibody MOv18 immunoglobulin G in ovarian carcinoma patients: A phase I study

Cancer ◽  
1997 ◽  
Vol 80 (S12) ◽  
pp. 2712-2720 ◽  
Author(s):  
Carla F.M. Moltoff ◽  
Helma M. Prinssen ◽  
Peter Kenemans ◽  
Arjan C. van Hof ◽  
Wim den Hollander ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Phase I ◽  
Ovarian Carcinoma ◽  
Immunoglobulin G ◽  
Phase I Study ◽  
Chimeric Monoclonal Antibody

Design and Construction of a Phosphorylatable Chimeric Monoclonal Antibody With a Highly Stable Phosphate

2004 ◽  
Vol 14 (11) ◽  
pp. 541-558 ◽  
Author(s):  
Wei Wu ◽  
John E. Kerrigan ◽  
Prem Yadav ◽  
Barbara Schwartz ◽  
Lara Izotova ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Chimeric Monoclonal Antibody ◽  
Design And Construction

MO283IMPACT OF VIS649, AN APRIL-NEUTRALIZING IGG2 MONOCLONAL ANTIBODY, ON TETANUS- AND DIPHTHERIA-TOXOID VACCINATION-ELICITED IMMUNE RESPONSES IN HEALTHY VOLUNTEERS: PHASE 1, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Jonathan Barratt ◽  
Mohit Mathur ◽  
Yusuke Suzuki ◽  
Frank Engler ◽  
Jill Yarbrough ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Intravenous Administration ◽  
Phase 1 ◽  
Study Drug ◽  
Fold Increase ◽  
Antibody Responses ◽  
Diphtheria Toxoid ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Serum Iga

Abstract Background and Aims VIS649, a humanized immunoglobulin G (IgG2) monoclonal antibody that binds to and blocks the biological actions of a proliferation-inducing ligand (APRIL), is in clinical development as a potential treatment for immunoglobulin A (IgA) nephropathy (IgAN). In a Phase 1 study, VIS649 was associated with dose-dependent reductions in serum IgA, IgG and IgM, which were reversible and showed a dose-response effect with respect to time-to-recovery. The aim of the present analysis was to determine if VIS649 suppression of APRIL influences antibody responses to tetanus and diphtheria toxoid vaccination. Method This was a Phase 1, randomized, double-blind, placebo-controlled, single ascending dose study of VIS649 in healthy adult male and female volunteers (ClinicalTrials.gov identifier: NCT03719443). In one cohort within the study, participants were randomized in a 2:1 ratio to receive intravenous administration of VIS649 6.0 mg/kg or placebo, followed by a vaccine composed of tetanus and diphtheria toxoids (TENIVAC®, Sanofi Pasteur Limited), in order to evaluate the effect of VIS649 on recipients’ ability to generate a vaccine booster response (exploratory endpoint). Participants received intravenous administration of study drug on Day 1, were discharged from the institution on Day 2, received a single intramuscular dose of vaccine at the Week 4 visit, and were followed for 16 weeks in total on an outpatient basis. Blood samples were taken at regular intervals, and anti-tetanus toxoid and anti-diphtheria toxoid IgG, IgM and IgA quantitative ELISA assays were performed. Tetanus and diphtheria anti-toxoid IgG titers ≥0.1 IU/mL are generally considered to be protective. Results In the vaccination cohort, 15 participants were randomized and dosed with study drug or placebo, of whom 14 completed the study, and one participant who received VIS649 was lost to follow-up prior to receiving the vaccine. Both groups (placebo and VIS649) demonstrated increased tetanus anti-toxoid IgG titers following immunization, with a mean 7.9-fold increase in IU/mL at Week 6 for placebo recipients and a mean 6.4-fold increase in IU/mL for VIS649 recipients (Figure). At visits after Week 6, tetanus anti-toxoid IgG titers declined faster in the VIS649 group than in the placebo group (consistent with the reduction in total IgG associated with VIS649 administration) but remained above the protective threshold of 0.1 IU/mL for all participants throughout the study. Similar trends were observed for diphtheria anti-toxoid IgG titers, with a mean 5.5-fold increase in IU/mL at the Week 6 visit for placebo recipients and a mean 5.1-fold increase for VIS649 recipients (Figure). There was no evidence of tetanus- or diphtheria-toxoid elicited IgM responses in either the placebo or VIS649 groups, consistent with the recall nature of the vaccination. In a post hoc analysis, pre-existing serum tetanus/diphtheria anti-toxoid IgA titers fell between Day 1 and Week 4 in the VIS649 group, consistent with the overall suppression of total serum IgA, were boosted after vaccination in both groups, and declined faster in the VIS649 recipients thereafter. Conclusion VIS649 treatment did not interfere with participants’ ability to mount an antigen-specific serum IgG or IgA boost response to tetanus and diphtheria toxoid vaccination. There was no evidence of tetanus- or diphtheria-specific IgM responses in either the placebo or VIS649 groups, consistent with recall vaccination exposure. These data indicate that qualitative antibody responses are preserved during APRIL suppression.

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