Boston University

Boston Medical Center Corporation

Northeastern University

Dana-farber-cancer Institute Inc.

David H Sherr

George J Murphy

Sarah S Rozelle

Brenden W Smith

Joshua Robert Giguere

Scott Edward Schaus

Michael Pollastri

Jennifer Schlezinger

Sarah Haigh Molina

Lee M Nadler

Joachim L Schultze

Robert H Vonderheide

Britta Maecker

Michael Bergwelt-Baildon

This disclosure provides methods of making a megakaryocyte-erythroid progenitor cell (MEP), comprising differentiating a MEP precursor cell into a MEP in culture in the presence of an aryl hydrocarbon receptor (AhR) modulator. In some embodiments the AhR modulator is an AhR antagonist. In some embodiments the AhR modulator is an AhR agonist. In some embodiments the methods comprise culturing MEP precursor cells in the presence of an AHR antagonist and then culturing MEP precursor cells in the presence of an AHR agonist. In some embodiments the stem cell is a pluripotent stem cell. In some embodiments the MEP co-expresses CD41 and CD235. In some embodiments the number of MEPs produced in the culture increases exponentially. Methods of making a red blood cell (RBC) by culturing a MEP in the presence of an AhR modulator are also provided. Methods of making a megakaryocyte and/or a platelet, comprising culturing a MEP in the presence of an AhR modulator are also provided. In some embodiments the AhR modulator is an AhR antagonist. This disclosure also provides compositions comprising at least 1 million MEPs per ml and compositions in which at least 50% of the cells are MEPs, among other things.

Production of red blood cells and platelets from stem cells

This disclosure provides methods of making a megakaryocyte-erythroid progenitor cell (MEP), comprising differentiating a stem cell into a MEP in culture in the presence of an aryl hydrocarbon receptor (AhR) agonist. In some embodiments the stem cell is a pluripotent stem cell. In some embodiments the MEP co-expresses CD41 and CD235. In some embodiments the number of MEPs produced in the culture increases exponentially. Methods of making a red blood cell (RBC) by culturing a MEP in the presence of an AhR agonist are also provided. Methods of making a megakaryocyte and/or a platelet, comprising culturing a MEP in the presence of an AhR modulator are also provided. In some embodiments the AhR modulator is an AhR antagonist. This disclosure also provides compositions comprising at least 1 million MEPs per ml and compositions in which at least 50% of the cells are MEPs.

Provided herein are novel agents that modulate AhR activity for use in therapeutic compositions and methods thereof for inhibiting cancer cell proliferation and tumor cell invasion and metastasis. The agents comprise AhR inhibitors or non-constitutive AhR agonists of Formula (I) and (II) for the inhibition of cancer cell growth and parameters that characterize tumor metastasis, such as tumor cell invasiveness.

Aryl hydrocarbon receptor (AhR) modifiers as novel cancer therapeutics

The invention provides methods for conducting cancer immunotherapy and diagnosis using cytochrome P450 1B1 and peptide fragments thereof.

Cancer immunotherapy and diagnosis using cytochrome P450 1B1

Growing community of inventors

West Roxbury, MA, United States of America

David H Sherr