Linking antibody sequences to function at the single-cell level using nanovial technology

NIH Pandemic-Era Grants

Pandemic Era Grants

2024

Document text

Principal Investigator: Joseph  de Rutte
Organization: PARTILLION BIOSCIENCE CORPORATION
Fiscal Year: 2024
Award: $731,568
Funding agency: National Institute of General Medical Sciences

ABSTRACT
Monoclonal antibody therapies now account for the majority of blockbuster drugs and the number and breadth
of diseases tackled by this therapeutic modality are expected to rapidly grow in the coming decade. However,
existing discovery technologies force users to choose between performance and cost. There is a need for
advanced discovery tools that provide a better functional picture of performance during initial high-throughput
screening. An ideal solution that can democratize antibody discovery would also be easily accessible, leveraging
existing equipment in pharmaceutical, biotech, and research laboratories. Partillion is developing and
commercializing a specialized hydrogel microparticle reagent (“nanovials”) that enables ultra high-throughput
sorting of single antibody secreting cells based on functional properties of secreted antibodies, all using standard
lab equipment and widely-available flow cytometers. Expanding on Phase I work and successful demonstration
of antibody discovery from plasma cells based on antigen-specific binding, in this Phase II proposal Partillion will
develop nanovial workflows to enable single-cell functional assays (binding of secreted antibodies to cell-surface
expressed targets and receptors that triggers signaling pathway activation) for our end users. These capabilities
can provide dramatic improvements in discovery workflows by minimizing the number of non-functional
sequences that have to be synthesized, introduced into cell lines, produced, and tested in large well-plate formats
downstream. Here we propose to develop on-nanovial functional screening assays for (i) binding to cell-surface-
expressed targets and (ii) receptor agonism, and benchmark the antibody sequences discovered with these
approaches against sequences recovered using standard hybridoma, and direct B cell Receptor (BCR) antigen
baiting workflows. Enabling more companies and institutes to access cutting-edge drug discovery capabilities
economically will also drive further development of therapeutic candidates for rare diseases and more crowded
“common diseases”, which ultimately will yield cost savings to the health systems and better outcomes for more
patients.

Terms: <Adoption><Affinity><Agonist><Antibodies><Antibody Diversity><Antibody Repertoire><Antibody-Secreting Cells><Antigen Targeting><Antigens><Assay><Autoimmune Diseases><B cell receptor><B-Cell Antigen Receptor><Bacteriophages><Benchmarking><Best Practice Analysis><Binding><Binding Proteins><Bioassay><Biological Assay><Biotech><Biotechnology><Blood Plasma Cell><Body Tissues><Bp35><CD 120a Antigen><CD120a Antigens><CD20><COVID-19><CV-19><Cancers><Capital><Cell Body><Cell Communication and Signaling><Cell Isolation><Cell Line><Cell Segregation><Cell Separation><Cell Separation Technology><Cell Signaling><Cell Surface Antigens><Cell membrane><Cell surface><CellLine><Cells><Cellular Assay><Chromium><Coronavirus Infectious Disease 2019><Cost Savings><Cr element><Crowding><Cytoplasmic Membrane><Data><Democracy><Development><Disease><Disorder><Drugs><Equipment><Expenditure><Genomics><Health system><High Throughput Assay><Hybridomas><Hydrogels><Immunization><Immunochemical Immunologic><Immunoglobulin-Secreting Cells><Immunologic><Immunologic Surface Markers><Immunological><Immunological Surface Markers><Immunologically><Immunologics><Incubated><Interview><Intracellular Communication and Signaling><Label><Laboratory Research><Leu-16><Ligand Binding Protein><Ligand Binding Protein Gene><Light><Link><MS4A1><MS4A1 gene><MS4A2><Malignant Neoplasms><Malignant Tumor><Marketing><Medication><Membrane><Methodology><Microfluidics><Modality><Modeling><Molecular Interaction><Monoclonal Antibody Therapy><Orphan Disease><Outcome><Patients><Performance><Phages><Pharmaceutical Agent><Pharmaceutical Preparations><Pharmaceuticals><Pharmacologic Substance><Pharmacological Substance><Phase><Photoradiation><Plasma Cells><Plasma Membrane><Plasmacytes><Process><Property><Protein Binding><Rare Diseases><Rare Disorder><Reagent><Receptor Protein><Receptor Signaling><Reporter><Research><Running><SBIR><Scientist><Side><Signal Pathway><Signal Transduction><Signal Transduction Systems><Signaling><Single cell seq><Small Business Innovation Research><Small Business Innovation Research Grant><Sorting><Strains Cell Lines><Surface Antigens><System><TNF Receptor p55><TNF-sR55><TNF-α receptor><TNFAR><TNFR p60><TNFR, 55-kD><TNFR, 60-kD><TNFR-I><TNFR1><TNFR55><TNFR60><TNFRSF1A><TNFRSF1A Receptor><TNFRSF1A gene><TNFalpha receptor><TNFα receptor><Technology><Testing><Therapeutic><Tissues><Training><Tube><Tumor Necrosis Factor Receptor 1><Tumor Necrosis Factor Receptor 55><Viral Diseases><Virus Diseases><Work><Yeasts><antagonism><antagonist><autoimmune condition><autoimmune disorder><autoimmunity disease><bacterial virus><benchmark><biological signal transduction><bound protein><cell assay><cell sorting><commercialization><coronavirus disease 2019><coronavirus disease-19><coronavirus infectious disease-19><cost><cultured cell line><developmental><drug discovery><drug/agent><fluorescence activated cell sorter><fluorescence activated cell sorter device><high throughput screening><immunogen><improved><instrument><lab equipment><laboratory equipment><laboratory technology><mAB-based therapy><mAb therapy><mAb-based therapeutics><malignancy><membrane structure><neoplasm/cancer><orphan disorder><particle><pharmaceutical><plasmalemma><plasmocyte><receptor><screening><screenings><single cell next generation sequencing><single cell sequencing><therapeutic agent development><therapeutic candidate><therapeutic development><therapeutic target><tool><tumor necrosis factor alpha receptor><tumor necrosis factor receptor 1A><tumor necrosis factor α receptor><viral infection><virus infection><virus-induced disease><µfluidic>