Bispecific and multispecific antibodies as a therapeutic strategy in respiratory diseases

Bispecific are biologics engineered to engage two distinct antigens or epitopes simultaneously. They have emerged as a powerful therapeutic modality across immune-mediated disease, initially in the oncology space and now with increasingly focus of this innovation in inflammation and immunity, including respiratory diseases. By enabling simultaneous neutralization of parallel inflammatory pathways (e.g., dual cytokine blockade in asthma, COPD, and pulmonary fibrosis), bispecific antibodies and antibody-based formats offer the potential for improved efficacy over single-target biologics, particularly in heterogeneous respiratory conditions where redundant or compensatory signaling limits monotherapy responses.Realizing this potential, however, requires navigating a distinct set of scientific and translational challenges relative to conventional monospecific antibodies. These include complex target-mediated drug disposition (TMDD) arising from receptor binding, format-dependent differences in valency and geometry, immunogenicity risks associated with novel molecular architectures, engineering trade-offs in half-life extension, delivery approaches (systemic vs. inhaled) and manufacturability constraints unique to multi-domain constructs. Understanding how these factors interact to shape clinical efficacy and safety in respiratory disease is essential for the rational design and development of next-generation bispecific therapeutics.This Research Topic invites contributions that advance the scientific, translational, and clinical understanding of bispecific biologics for respiratory diseases, including but not limited to asthma, chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and other inflammatory or fibrotic lung conditions.We welcome Original Research, Review, Mini Review, Perspective, Systematic Review, and Case Reports addressing, but not limited to, the following themes:• Target biology: Rationale and evidence for dual-pathway or dual-epitope targeting in respiratory disease; comparative efficacy of bispecific versus monospecific approaches; biomarker-driven patient stratification.• Current Clinical Evidence: Review of clinical studies or other sources that provide validation of synergy or additive effect of combination therapies. • Research that enables a better understanding of the rationale for combining two or more targets, explore what is the residual unmet need after having multiple approved biologics available for respiratory diseases.• Evidence that explores the true T2 patients not covered by the existing biologics and if there is a mixed endotype targetable.• Guidance or decision tree to select multiple targets. Evidence from models to real life experience. • Pharmacokinetic/pharmacodynamic modeling of bispecific constructs with dual-target engagement; mechanistic and quantitative approaches to characterizing and predicting exposure in respiratory tissue and systemic compartments. • Differences in targeting IL-13 versus IL4-RA.• Biologic and bispecific formats: Comparative analysis of bispecific architectures (e.g., IgG-like, tandem scFv, DVD-Ig, common light chain, Fab-based, nanobody-based, and other emerging formats) and their suitability for pulmonary delivery and target engagement. This section also seeks further understanding of the challenges and opportunities of co-administrations of biologics in relation to bispecifics. • Immunogenicity: Risk factors and mitigation strategies for anti-drug antibody responses associated with novel bispecific architectures; assay strategies for immunogenicity assessment.• Half-life extension: Engineering strategies (e.g., FcRn engagement, albumin binding, PEGylation, Fc modifications) and their impact on pharmacokinetics, dosing frequency, and lung tissue exposure.• Manufacturability and CMC challenges: Chain pairing and mispairing issues, aggregation propensity, purification complexity, and formulation strategies unique to multi-specific constructs; approaches to improving developability.• Safety: Preclinical and clinical safety findings, on-target/off-tissue toxicity considerations, and risk assessment frameworks specific to bispecific mechanisms of action in respiratory indications.We encourage submissions spanning discovery research, translational and preclinical studies, clinical trial data, computational and modeling approaches, and critical reviews that synthesize the current state of the field and identify open questions and future directions. Topic editors: Hector Ortega, Arnaud Bourdin Source: https://www.frontiersin.org/research-topics/86977/bispecific-and-multispecific-antibodies-as-a-therapeutic-strategy-in-respiratory-diseases