Washington University

John DiPersio

Matthew Cooper

Alun Carter

Stephen Persaud

Among the various aspects of the present disclosure is the provision of conditioning agents for use in allogeneic hematopoietic stem cell transplantation. An aspect of the present disclosure provides for a method of treating a subject or inhibiting alloreactivity in the host-versus-graft direction comprising administering a combination of conditioning agents comprising an anti-body-drug conjugate (ADC) and a JAK1/JAK2 inhibitor for use in allogeneic hematopoietic stem cell transplantation in an amount sufficient to permit engraftment of allogeneic bone marrow. In some embodiments, the ADC is selected from CD45-SAP, cKit-SAP, CD117-Amanitin, and CD45-PBD. In some embodiments, the JAK1/JAK2 inhibitor is selected from baricitinib and ruxolitinib. In some embodiments, the method further comprises administering a cancer therapeutic.

Conditioning agents for use in allogeneic hematopoietic stem cell transplantation

Disclosed herein are methods of gene editing, or endogenous suppression, of cytokines/chemokines/transcription factors secreted from chimeric antigen receptor (CAR)-bearing immune effector cell such as CAR-T cells for the mitigation of cytokine release syndrome and/or CAR-T associated neuropathy. These methods involve insertion of the CAR into a locus of a cytokine gene, blocking its expression. Also disclosed herein are (CAR)-bearing immune effector cells with CARs inserted into a locus of a cytokine gene, and methods of treatment of diseases with immunotherapy with a reduced incidence of cytokine release syndrome and/or CAR-T associated neuropathy.

Growing community of inventors

St. Louis, MO, United States of America

John DiPersio