Approximately 25% of the products being developed by the biotechnology industry are antibodies and many of these antibodies are directed to epitopes on human cells and tissues. We are proposing a novel concept for the production of antibodies with therapeutic potential that is based on recent advances in protein-protein interactions and recent developments in transgenic technology. Execution of this concept will obviate many of the expensive and time consuming modifications that are frequently required after potentially therapeutic monoclonal antibodies are identified in order to optimize their pharmacological properties and to make them amenable to large scale production. By combining recent data derived from in vitro studies with the nascent understanding of genomics, we will extend the range of epitopes that can be accessed and, therefore, extend the range of potentially therapeutic antibodies
Public Health Relevance: During the past 15 years, more than 20 therapeutic antibodies have been developed to treat human disease, particularly in the fields of automimmunity and cancer. We have proposed a novel method to obtain potentially therapeutic antibodies that will recognize targets that cannot be obtained from conventional sources. In addition, the technology will engineer antibodies that have improved pharmacological attributes and better manufacturing properties. This technology will provide a cost-effective route to increasing the range of therapeutic candidates for the treatment of human disease.
Public Health Relevance Statement: During the past 15 years, more than 20 therapeutic antibodies have been developed to treat human disease, particularly in the fields of automimmunity and cancer. We have proposed a novel method to obtain potentially therapeutic antibodies that will recognize targets that cannot be obtained from conventional sources. In addition, the technology will engineer antibodies that have improved pharmacological attributes and better manufacturing properties. This technology will provide a cost-effective route to increasing the range of therapeutic candidates for the treatment of human disease.
Project Terms: ATGN; Animals; Antibodies; Antibody Affinity; Antibody Formation; Antibody Production; Antibody Response; Antigenic Determinants; Antigens; Aves; Avian; B blood cells; B-Cells; B-Lymphocytes; Binding Determinants; Biotechnology; Birds; Body Tissues; Bovine Species; Bursa-Dependent Lymphocytes; Bursa-Equivalent Lymphocyte; CDR; Callicrein; Cancers; Cattle; Cell Line; Cell Lines, Strains; CellLine; Cells; Chickens; Complementarity Determining Regions; Complimentarity Determining Region; D-Mannose; DNA Polymerase Delta Auxiliary Protein; DNA-Dependent RNA Polymerase II; Data; Development; EYDF; Engineering; Engineerings; Epitopes; Framework Regions; Gallus domesticus; Gallus gallus; Gallus gallus domesticus; Gene Conversion; Genes, Ig; Genes, Immunoglobulin; Genetic Engineering of Proteins; Genome; Genomics; Hu-mABs; Human; Human Engineering; Human, General; Humulin R; Hypervariable Loop; Hypervariable Regions; Hypoxia Inducible Factor; IGH; IGH@ gene cluster; IgH locus; Immune system; Immunization; Immunoglobulin Genes; Immunoglobulin Heavy Chain Genes; Immunoglobulin Heavy Gene; Immunoglobulin Heavy Locus; Immunoglobulin Hypervariable Region; Immunologic Stimulation; Immunological Stimulation; Immunostimulation; In Vitro; Industry; Insulin; Insulin (ox), 8A-L-threonine-10A-L-isoleucine-30B-L-threonine-; Insulin, Regular; Kallidinogenase; Kalliginogenase; Kallikreins; Kinin-Forming Enzyme; Kininogenase; Knock-in; Knock-in Mouse; L-Serine; L-Tryptophan; L-Tyrosine; Levotryptophan; Light; MAb Therapeutics; Malignant Neoplasms; Malignant Tumor; Mammalia; Mammals; Mammals, General; Mammals, Mice; Mammals, Rabbits; Man (Taxonomy); Man, Modern; Mannopyranose; Mannopyranoside; Mannose; Melatonin Receptors; Methods; Mice; Moab, Clinical Treatment; Modification; Monoclonal Antibodies; Murine; Mus; Novolin R; Oryctolagus cuniculus; PCNA-Cyclin; Peptides; Phase; Photoradiation; Phylogenetic Analysis; Phylogenetics; PrP Proteins; Primordial Germ Cell; Prion Proteins; Prions; Proliferating Cell Nuclear Antigen; Property; Property, LOINC Axis 2; Protein Engineering; Proteins; Pseudogenes; RNA Polymerase B; RNA Polymerase II; Rabbit, Domestic; Rabbits; Reagent; Regions, Framework; Route; Sensitization, Immunologic; Sensitization, Immunological; Serine; Source; Specificity; Structure of primordial sex cell; TYR; Technology; Testing; Therapeutic; Therapeutic Monoclonal Antibodies; Therapeutic antibodies; Time; Tissues; Transgenic Animals; Transgenic Organisms; Tryptophan; Tyrosine; Tyrosine, L-isomer; activin A; antibody biosynthesis; antibody engineering; antigen antibody affinity; base; body system, allergic/immunologic; bovid; bovine; cost; cow; cultured cell line; cystatin C; erythroid differentiation factor; erythroid differentiation protein; experiment; experimental research; experimental study; gene product; homo-activin A; homologous recombination; human disease; human monoclonal antibodies; immunogen; immunoglobulin biosynthesis; immunoglobulin heavy chain locus; improved; kininogenin; large scale production; malignancy; meetings; neoplasm/cancer; novel; organ system, allergic/immunologic; para-Tyrosine; polyclonal antibody; post gamma-globulins; post-gamma-protein; protein protein interaction; public health relevance; research study; therapeutic target; transgenic; vector
