Leventhal, D. S. | Search bioRxiv

bioRxiv2025

The Immunogenicity Database Collaborative (IDC): A Standardized, Publicly Available Database for Clinical Immunogenicity Observations and Insights

The incidence and impact of anti-drug antibodies (ADAs) against biotherapeutics remain difficult to predict, limiting efforts to mitigate immunogenicity risk prior to clinical trials. Existing data are fragmented across disparate sources with inconsistent definitions, representing a key barrier to progress in the field. Here, we present the Immunogenicity Database Collaborative (IDC) and its release of the Immunogenicity Database (DB) V1: a structured clinical immunogenicity dataset integrating therapeutic characteristics, sequence, and patient cohort-level data from publicly available sources. The dataset includes 4,146 ADA datapoints, 1,788 cohorts, 727 clinical trials and 218 therapeutics. We highlight trends in ADA incidence, evaluate sources of variability, and identify driving factors of immunogenicity risk. This work provides a foundational resource to standardize and support immunogenicity risk assessment across the industry. It also provides an initial data architecture and invites the research community to contribute towards future expansions of the database into key areas of interest to the field.

pharmacology and toxicology↗

bioRxiv2024

Synthetic bacteria with programmed cell targeting and protein injection suppress tumor growth in vivo

Bacterial living therapeutics (BLTs) hold promise for treating cancer and other human diseases because they can be engineered and transported into the microbiota (e.g., of tumors, gastrointestinal tract) to deliver therapeutic payloads. Current approaches rely on the natural tropism of the bacterial chassis used and trigger the local release of protein cargoes, typically through active extracellular secretion or bacterial lysis. BLTs capable of targeting specific cellular subsets and delivering payloads intracellularly might provide new therapeutic opportunities and improve efficacy while reducing off-target effects. We used synthetic biology to develop BLTs that can deliver defined cargo proteins into the cytoplasm of target cells. We designed a modular synthetic bacterium with programmed adhesion to cells by targeting defined cell surface antigen and armed with an inducible type III secretion system (T3SS) for injection of a protein cargo of interest. As a proof of principle, we programmed synthetic bacteria to recognize the epidermal growth factor receptor (EGFR) and inject the catalytic fragments of the potent adenosine diphosphate-ribosyltransferase toxins ExoA and TccC3. These BLTs demonstrated the ability to trigger robust tumor cell death in vitro. Intratumoral administration of these synthetic bacteria suppressed tumor growth in vivo and prolonged the survival of treated animals when the tumor cells were recognized by the engineered bacteria. These results demonstrate the potential of programming cell targeting and controlled protein injection for the development of effective and specific BLTs. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=108 SRC="FIGDIR/small/590337v1_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@eb769dorg.highwire.dtl.DTLVardef@b84b39org.highwire.dtl.DTLVardef@152b8b0org.highwire.dtl.DTLVardef@1db4108_HPS_FORMAT_FIGEXP M_FIG C_FIG

synthetic biology↗