Int Immunopharmacol
Pharmacokinetics, Dynamics, and Metabolism, Pfizer Inc., Andover, MA, United States.
Published: February 2014
The peptide-antibody (Ab) genetic fusion is a promising technology for targeting multiple antigens in a single Ab-like molecule. We have recently described generation and in vitro characterization of several such genetic fusions, using an interleukin (IL)-17A binding peptide and an anti-IL-22 Ab as a model system. In this study we assessed pharmacokinetic profiles of these model genetic fusions in mice. Specifically an IL-17A binding peptide was fused to either the heavy chain or both the heavy and the light chains of an anti-IL22 human IgG1 (referred to Compounds 1 or 2, respectively). Swiss Webster mice were given a single 10 mg/kg IV dose of Compound 1 or Compound 2 and serum concentrations were measured by a fused molecule immunoassay, in which IL-17A was used as a capture and anti-human IgG was used as a detector. In addition, serum samples were assayed using a total human IgG immunoassay. PK parameters were calculated by non-compartmental modeling. The two genetic fusions had similar PK profiles, with total body clearance of ~0.9-1.0 mL/h/kg, volume of distribution at steady-state of ~63-65 mL/kg, and elimination half-life of ~40 h. Our study provides the first characterization of the PK properties of peptide-Ab genetic fusions and suggests that although these genetic fusions appear to be eliminated faster than a typical Ab, the PK profile may be suitable for preclinical and clinical testing.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1016/j.intimp.2013.11.013 | DOI Listing |
Ann Hematol
January 2025
Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-Ku, Tokyo, 113-8677, Japan.
Donor cell leukemia (DCL), in which malignancy evolves from donor's stem cells, is an infrequent complication of allogeneic hematopoietic stem cell transplantation. Acute promyelocytic leukemia (APL) derived from donor cell is extremely rare and only four cases have been reported to date. Herein we report a case of donor cell-derived APL developing 32 months after haploidentical peripheral blood stem cell transplantation using posttransplant cyclophosphamide for myelodysplastic syndromes.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114.
Ependymoma (EPN) is a common form of brain tumor in children, often resistant to available cytotoxic therapies. Molecular profiling studies have led to a better understanding of EPN subtypes and revealed a critical role of oncogenes ZFTA-RELA fusion and EPHB2 in supratentorial ependymoma (ST-EPN). However, the immune system's role in tumor progression and response to therapy remains poorly understood.
View Article and Find Full Text PDFClin Transl Gastroenterol
January 2025
Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang province, China.
Background: Cholelithiasis is influenced by various factors, including genetic elements identified in genome-wide association studies (GWAS), but their biological functions are not fully understood.
Methods: Analyzing data from the Finngen database with 37,041 cholelithiasis cases and 330,903 controls, this study combined SNP data from GTEx v8 and linkage disequilibrium data from the 1000 Genomes Project. Using the TWAS FUSION protocol and SMR analysis, it investigated the relationship between gene expression and cholelithiasis, employing colocalization tests and conditional analyses to explore causality.
FASEB J
January 2025
Key Laboratory of Biomechanics and Mechanobiology, Ministry of Education, Key Laboratory of Innovation and Transformation of Advanced Medical Devices, Ministry of Industry and Information Technology, National Medical Innovation Platform for Industry-Education Integration in Advanced Medical Devices (Interdiscipline of Medicine and Engineering), School of Biological Science and Medical Engineering, Beihang University, Beijing, China.
The smooth muscle cells (SMCs) located in the vascular media layer are continuously subjected to cyclic stretching perpendicular to the vessel wall and play a crucial role in vascular wall remodeling and blood pressure regulation. Mesenchymal stem cells (MSCs) are promising tools to differentiate into SMCs. Mechanical stretch loading offers an opportunity to guide the MSC-SMC differentiation and mechanical adaption for function regeneration of blood vessels.
View Article and Find Full Text PDFThorac Cancer
January 2025
Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Background: The clinical implications of different EML4-ALK fusion variants remain poorly elucidated in the era of second-generation ALK inhibitors.
Methods: This was a retrospective cohort study, wherein patients diagnosed with locally advanced or metastatic non-small cell lung cancer harboring EML4-ALK fusion were stratified into two cohorts based on their first-line treatment: Cohort 1 received alectinib, while Cohort 2 received crizotinib. Statistical analysis was employed to investigate the impact of different EML4-ALK variants and TP53 status on the efficacy of first-line ALK-TKIs.
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!
© LitMetric 2025. All rights reserved.