摘要 |
The present invention is directed to novel chimeric proliferation receptor proteins and DNA sequences encoding these proteins where the chimeric proteins are characterized in three general categories. In one category, the novel chimeric proteins comprise at least three domains, namely, an extracellular inducer-responsive clustering domain capable of binding an extracellular inducer that transmits a signal to a proliferation signaling domain, a transmembrane domain and a proliferation signaling domain that signals a host cell to divide. In the second category, the novel chimeric proteins comprise at least two domains, namely, an intracellular inducer-responsive clustering domain capable of binding an intracellular inducer and a proliferation signaling domain that signals the cell to divide. In yet a third category, a novel hybrid chimeric protein receptor is contemplated that contains an intracellular or extracellular inducer domain, a transmembrane domain, a proliferation signaling domain and an effector signaling domain in a single chain molecule. Whether the binding domain is intracellular or extracellular, the binding of inducer to these novel chimeric receptor proteins induces the clustering of the binding domains to each other and further signals the cell to proliferate, and optionally, signal an effector function. The present invention further relates to expression vectors containing the nucleic acids encoding the novel chimeric receptors, cells expressing the novel chimeric receptors and therapeutic methods of using cells expressing these novel receptors for the treatment of cancer, infectious disease and autoimmune diseases, for example.
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