1. Selection of human anti-CD28 scFvs from a T-NHL related scFv library using ribosome display
- Author
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Barbara E. Power, Anne Nathanielsz, Frank Oberhäuser, Ralf J. Hosse, Achim Rothe, Elke Pogge von Strandmann, Peter J. Hudson, and Andreas Engert
- Subjects
Immunoassay ,biology ,Lymphoma, Non-Hodgkin ,Receptors, Antigen, T-Cell ,Antibodies, Monoclonal ,RNA ,CD28 ,chemical and pharmacologic phenomena ,Bioengineering ,General Medicine ,Applied Microbiology and Biotechnology ,Virology ,Immunoglobulin Fc Fragments ,Affinity maturation ,Immune system ,CD28 Antigens ,Antigen ,Peptide Library ,Ribosome display ,biology.protein ,Humans ,Antibody ,Peptide library ,Ribosomes ,Biotechnology - Abstract
Engineered antibodies have become an invaluable source of biopharmaceuticals against a wide range of diseases. About 200 antibody-based biologicals have been tested in clinical trials. Single chain variable fragments of antibodies (scFvs) provide binding specificity and offer an increased ease of in vitro display selection. Here, we present the generation of a human scFv library from peripheral blood lymphocyte RNA of a patient with relapsed T-cell non-Hodgkin lymphoma (T-NHL) who experienced a rare case of "spontaneous" remission. Antibodies against human T-cell antigen CD28, a co-stimulatory protein that influences the immune response by amplification of the transcriptional effects of T-cell receptors, might have contributed to the patient's remission. The scFv library was panned against CD28 using ribosome display and further subjected to affinity maturation. Isolated scFv were assessed for binding specificity and affinity and may provide the basis for the development of novel immunotherapeutic strategies. This work demonstrates the selection of a fully human antibody fragment from a patient-derived gene pool by in vitro ribosome display technology.
- Published
- 2007