METHODS AND COMPOSITIONS RELATED TO MODULATORS OF EUKARYOTIC CELLS

摘要

Methods for Identifying protein modulators of eukaryotic cells by expressing a combinatorial library of potential agonists inside a eukaryotic cell and then directly selecting for an agonist of a target molecule. Some methods involve co-culturing a cell expressing a combinatorial library of potential agonists and a second cell, and then selecting agents that modulate a phenotype of or a desired cellular response in the second cell. Preferably, the agonists are antibodies introduced into and expressed in the starting cells, such as agonist anti-EpoR, anti-TpoR, or G-CSFR antibodies. Also disclosed are methods for selecting from combinatorial antibody libraries bispecific antibodies that can regulate cell phenotypes.

主权项

1. A method for identifying a modulator antibody of a phenotype of a eukaryotic cell type, comprising (a) expressing in a population of cells of the eukaryotic cell type a library of candidate antibodies or antigen-binding fragments thereof to produce a heterogeneous population of modified, antibody-expressing cells, and (b) selecting a specific antibody-expressing cell with an altered phenotype relative to that of an unmodified control cell of said eukaryotic cell type; thereby identifying the candidate antibody expressed in the specific antibody-expressing cell as a modulator of the eukaryotic cell type.