Widespread drug resistance due to empiric use of broad-spectrum antibiotics has stimulated development of bacteria-specific strategies for prophylaxis and therapy based on modern monoclonal antibody (mAb) technologies. However, single-mechanism mAb approaches have not provided adequate protective activity in the clinic. We constructed multifunctional bispecific antibodies, each conferring three mechanisms of action against the bacterial pathogen Pseudomonas aeruginosa by targeting the serotype-independent type III secretion system (injectisome) virulence factor PcrV and persistence factor Psl exopolysaccharide. A new bispecific antibody platform, BiS4, exhibited superior synergistic protection against P. aeruginosa-induced murine pneumonia compared to parent mAb combinations or other available bispecific antibody structures. BiS4αPa was protective in several mouse infection models against disparate P. aeruginosa strains and unexpectedly further synergized with multiple antibiotic classes even against drug-resistant clinical isolates. In addition to resulting in a multimechanistic clinical candidate (MEDI3902) for the prevention or treatment of P. aeruginosa infections, these antibody studies suggest that multifunctional antibody approaches may be a promising platform for targeting other antibiotic-resistant bacterial pathogens.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1126/scitranslmed.3009655 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Bispecific Antibodies for Lymphoid Malignancy Treatment.
Cancers (Basel)
December 2024
Hematology Division, A.O.U. Città della Salute e della Scienza di Torino, C.so Bramante 88, 10126 Turin, Italy.
Backgroud: The introduction of highly active immunotherapies has changed the outcome of B-cell non-Hodgkin lymphomas (B-NHLs) in the last two decades. Since then, important progress has been shown using newer and more active immunotherapies, including chimeric antigen receptor T-cell therapy (CAR-T), conjugated monoclonal antibodies, and bispecific antobodies, which currently plays a significant role in the treatment of diffuse large B-cell (DLBCL), follicular (FL), and mantle cell (MCL) lymphoma.
Purpose: In this review, we provide an updated overview of recently completed and ongoing BsAb trials in patients with relapsed/refractory(R/R) B-NHL and Hodgkin's lymphoma, including single-agent results, emerging combinations, safety data, and novel constructs.
Immune-modulating nanomedicines for enhanced drug delivery to non-small-cell lung cancer.
Biomaterials
January 2025
Centre for Advanced Imaging (CAI), Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, Brisbane, QLD, 4072, Australia; ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, The University of Queensland, Brisbane, QLD, 4072, Australia; ARC Training Centre for Innovation in Biomedical Imaging Technology, University of Queensland, QLD, Australia. Electronic address:
Immune-modulating peptides have shown potential as novel immune-stimulating agents which enhance the secretion of anticancer cytokines in vitro. However, fast clearance from blood hampers the ability of such peptides to accumulate in the tumour and results in limited therapeutic efficacy in animal studies. To address the fast blood clearance, this work reports the development and validation of a novel polymeric nanoparticle delivery system for the efficient localization of an immunomodulating peptide in the tumour microenvironment (TME).
View Article and Find Full Text PDFPatients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) have poor outcomes. Gemcitabine + oxaliplatin (GemOx) with rituximab, a standard salvage therapy, yields complete response (CR) rates of approximately 30% and median overall survival (OS) of 10-13 months. Patients with refractory disease fare worse, with a CR rate of 7% for subsequent therapies and median OS of 6 months.
View Article and Find Full Text PDFDecoupling Individual Host Response and Immune Cell Engager Cytotoxic Potency.
ACS Nano
January 2025
Aix-Marseille Univ., CNRS, INSERM, LAI, Centuri Living Systems, 13009 Marseille, France.
Immune cell engagers are molecular agents, usually antibody-based constructs, engineered to recruit immune cells against cancer cells and kill them. They are versatile and powerful tools for cancer immunotherapy. Despite the multiplication of engagers tested and accepted in the clinic, how molecular and cellular parameters influence their actions is poorly understood.
View Article and Find Full Text PDFRisk of infections in bispecific antibody therapy for multiple myeloma: a comprehensive review of literature.
Hematology
December 2025
Clinical Pharmacy Department, King Fahad Medical City, Riyadh, RH, Saudi Arabia.
Multiple Myeloma (MM) is a malignancy characterized by abnormal production of monoclonal immunoglobulins in plasma cells. Bispecific antibodies have emerged as a significant advancement in MM treatment, offering high effectiveness and specificity by targeting different antigens such as BCMA, CD38, and FcRH5. However, the risk of infection poses a major challenge in MM patients, which is thought to be influenced by various factors.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!