Methods and compositions related to modulators of eukaryotic cells

A method for identifying an antibody or antigen-binding fragment thereof capable of reprograming or trans-differentiating a eukaryotic target cell, comprising

• (1) expressing a library of either (i) secreted candidate antibodies or antigen-binding fragments thereof in a reporter cell bearing a signaling receptor expressed by the target cell to produce a heterogeneous population of modified, antibody or antigen-binding fragment thereof-expressing reporter cells, wherein the cells are cultured in a diffusion restricting culture medium such that the secreted antibodies or antigen-binding fragments thereof are trapped around the cells producing the secreted antibodies or antigen-binding fragments thereof, or (ii) membrane-integrated candidate antibodies or antigen-binding fragments thereof in a reporter cell bearing a signaling receptor expressed by the target cell to produce a heterogeneous population of modified, antibody or antigen-binding fragment thereof-expressing reporter cells, wherein the entire membrane-integrated antibody or antigen-binding fragment thereof library and the signaling receptor are co-integrated into the plasma membrane of the population of reporter cells;
• (2) identifying, in an autocrine manner, a subpopulation of antibody or antigen-binding fragment thereof-expressing reporter cells with activated signaling of the receptor,
• (3) isolating a group of agonist antibodies or antigen-binding fragments thereof from the identified subpopulation of cells, and
• (4) contacting the group of agonist candidate antibodies or antigen-binding fragments thereof with a population of the target cell and selecting a cell with a specific phenotype indicative of trans-differentiation;
• thereby identifying an antibody or antigen-binding fragment thereof capable of reprograming or trans-differentiating the target cell.