Multispecific chimeric receptors

摘要

Novel multispecific chimeric receptor DNA sequences, expression cassettes and vectors containing these sequences as well as cells containing the chimeric DNA and novel chimeric receptor proteins expressed from the sequences are provided in the present invention. The novel multispecific chimeric receptor DNA and amino acid sequences comprise at least three domains that do not naturally exist together: (1) a multispecific binding domain comprising at least two extracellular inducer-responsive clustering domains which serves to bind at least one specific inducer molecule, (2) a transmembrane domain, which crosses the plasma membrane, and (3) either a proliferation signaling domain that signals the cell to divide, or an effector function signaling domain which directs a host cell to perform its specialized function. Optionally, all the multispecific chimeric receptors may contain one or more intracellular inducer-responsive clustering domains attached to one or more of the cytoplasmic signaling domains or the transmembrane domain. The present invention also relates to novel hybrid multispecific chimeric receptors comprising at least one proliferation signaling domain and at least one effector function signaling domain together on the multispecific receptor molecule. The present invention further relates to therapeutic methods and strategies that employ the cells expressing these novel chimeric receptors for the treatment of cancer, infectious disease and autoimmune disease which may have greater therapeutic benefit over a combination of drug therapies.