Methods and compositions for use of therapeutic t cells in combination with kinase inhibitors

Abstract

The present disclosure relates to methods, compositions and uses involving immunotherapies and inhibitors of a target protein tyrosine kinase in which the kinase is not IL-2-inducible T cell kinase (ITK) and/or is selected from Bruton's tyrosine kinase (BTK), tec protein tyrosine kinase (TEC), BMX non-receptor tyrosine kinase (Etk), TXK tyrosine kinase (TXK) and/or receptor tyro-sine-protein kinase ErbB4 (ErbB4). The provided methods, compositions and uses include administration of one or more such inhibitor with another agent, such as an immunotherapeutic agent targeting T cells and/or genetically engineered T cells, such as CAR-expressing T cells. Also provided are methods of manufacturing engineered cells, cells, compositions, methods of administration, nucleic acids, articles of manufacture and kits. In some aspects, features of the methods and cells provide for improved activity, efficacy, persistence, expansion and/or proliferation of T cells for adoptive cell therapy or endogenous T cells recruited by immunotherapeutic agents.