The invention provides methods for identifying protein modulators (e.g., antibody agonists) of eukaryotic cells. The methods typically involve expressing a combinatorial agent library (e.g., via lentiviral vectors) inside a eukaryotic cell type (e.g., a mammalian cell) and then directly selecting for agents (e.g., antibodies) that are agonist of a target molecule (e.g., a signaling receptor) that modulates a phenotype of or elicits a cellular response in the cell. Some related methods involve co-culturing a cell expressing a combinatorial agent library and a second cell, and then selecting agents that modulate a phenotype of or elicit a cellular response in the second cell. Preferably, the agents are antibodies and are introduced into and expressed in the starting cells under conditions each individual cell expresses no more than 3 different members of the antibody library. In addition, the invention provides methods for identifying protein agonists that capable of reprograming or trans-differentiating a target cell. Also provided in the invention are specific agonist antibodies of signaling receptors or biomolecules that modulate a phenotype or effectuate a cellular response in a eukaryotic cell (e.g., agonist antibodies of EpoR, TpoR or G-CSFR). Further provided in the invention are methods for selecting from combinatorial antibody libraries bispecific antibodies that can regulate cell phenotypes.

Provided herein are immunomodulatory proteins comprising variant PD-L1 and nucleic acids encoding such proteins. The immunomodulatory proteins provide therapeutic utility for a variety of immunological and oncological conditions. Compositions and methods for making and using such proteins are provided.

The present invention discloses cell lines and recombinant growth factor receptors useful in adoptive cell therapy (ACT), wherein the recombinant growth factor receptor can act as a molecular switch enabling cells expressing the rGFR protein to be expanded in-vitro or in-vivo. Thus the invention provides a T or NK cell, comprising a recombinant growth factor receptor (rGFR) comprising: (i) an extracellular (EC) domain; (ii) a thrombopoietin receptor transmembrane (TM) domain; and (iii) a growth factor receptor intracellular (IC) domain.

The present invention discloses cell lines and recombinant growth factor receptors useful in adoptive cell therapy (ACT), wherein the recombinant growth factor receptor can act as a molecular switch enabling cells expressing the rGFR protein to be expanded in-vitro or in- vivo. Thus the invention provides a T or NK cell, comprising a recombinant growth factor receptor (rGFR) comprising: (i) an extracellular (EC) domain; (ii) a thrombopoietin receptor transmembrane (TM) domain; and (iii) a growth factor receptor intracellular (IC) domain.

Provided herein are generalized extracellular molecule sensors (GEMSs) and polynucleotides encoding the GEMSs. Also provided herein are methods of making and using the GEMSs, such as therapeutic and diagnostic methods.

Provided herein are compositions and methods for promoting hematopoietic cell cytotoxicity.

The present invention relates to engineered extra-cellular vesicle internalizing receptors that have the ability to enhance uptake, processing, and presentation to T-cells of tumor-associated antigens by an antigen-presenting cell. It further relates to vectors or antigen presenting cells expressing said receptors, composition and uses thereof for the prevention and/or treatment of a cancer.

This disclosure relates to compositions and methods for treating cancer using chimeric antigen receptor T cells targeting glypican 3.

The present invention relates to methods of treating sclerotic conditions and more specifically to methods of treating chronic graft versus host disease with specific dosages of an anti-CSF-1R antibody, specifically axatilimab.

The present invention provides chimeric cytokine receptors, particularly chimeric cytokine receptors that canbe activated in tumor microenvironment, and their uses in tumor immunotherapy (e.g., adoptive cell therapy). The present invention further provides methods of genetically modifying therapeutic cells resulting in an enhanced immune response against a target antigen. The application further provides therapeutic cells that express said chimeric cytokine receptors and methods for treating patients using the modified therapeutic cells.