SBIR-STTR Award

Monoclonal antibodies have immense potential for use as prophylactic, diagnostic, and therapeutic agents in the treatment of various types of human aflments. For many uses it is desirable to use human monoclonal antibodies as opposed to murine monoclonal antibodies. Although many approaches have been attempted to produce human monoclonal antibodies, serious limitations have been encountered. The aim of the proposed research plan is to introduce human antibody genes into mice and to utilize the resultant transgenic mice to efficiently produce human monoclonal antibodies.Three questions will be addressed:(1) Will a germline mouse hnmunoglobulin gene, which has been introduced into a transgenic mouse, undergo in vivo rearrangement, somatic mutation, and heavy chain class switching?(2) Is there a functional relationship between homologous mouse and human variable region genes?(3) Will human germline immunoglobulin genes behave similarly to murine immunoglobulin genes when introduced into transgenic mice?

Monoclonal antibodies have great potential as a unique set of highly specific reagents for the prophylaxis, diagnosis and therapy of human diseases. However, a major problem encountered is the immunogenicity of these murine antibodies which limits their usefulness. In addition, human antibodies may be more efficient than mouse antibodies in mediating biological effector functions such as antibody-dependent cellular cytotoxicity in human patients. It would be a major advance to create a routine system for producing human monoclonal antibodies. The aim of our research is to generate a strain of transgenic mice that can rearrange human immunoglobulin genes, and thus, provide a functional human antibody repertoire. Mouse hybridomas could then be produced from such a mouse, using conventional techniques, that are producing human monoclonal antibodies.

Thesaurus Terms:
Animals, Chordates, Mammals, Rodents, Myomorpha, Mice (Laboratory) Animals, Transgenic Animals Biology, Systematic, Genetic Strains Biotechnology Blood Cells, B Lymphocytes Blood Cells, T Lymphocytes Cell Hybrids, Hybridomas Genetic Manipulation Genetic Manipulation, Transfection Genetics, Extrachromosomal Inheritance, Plasmids Genetics, Genes, Gene Expression Genetics, Genetic Regulation, Transcription Genetics, Recombination Globulins, Gamma Globulins, Immunoglobulin(S) Immunogenetics, Immunoglobulin Genes And Control Immunological Preparations, Monoclonal Antibodies Nucleic Acids, Dna Or Rna Insertionelements And Vectors Nucleic Acids, Mrna Tissue (Cell) CultureNational Institute of General Medical Sciences (NIGMS)