Methods and compositions for genetically modifying and expanding lymphocytes and regulating the activity thereof

A technology of lymphoid tissue and cells, applied in the field of immunology
CN111479921APending Publication Date: 2020-07-31埃克苏马生物技术公司
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Patent Information

Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
埃克苏马生物技术公司
Publication Date
2020-07-31

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Abstract

The present disclosure provides methods and compositions for genetically modifying lymphocytes and related methods that include genetically modifying T cells and / or NK cells. The methods use replication incompetent recombinant retroviral particles that comprise a pseudotyping element on their surface and optionally a membrane-bound T cell activation element, such as an anti-CD3, and encode one ormore engineered signaling polypeptides that can include a lymphoproliferative element, and / or a chimeric antigen receptor (CAR). The methods can include contacting PBMCs with replication incompetent recombinant retroviral particles for various exemplary time periods, such as less than 24 hours or in some illustrative embodiments less than 15 minutes. Illustrative chimeric lymphoproliferative elements that are capable of promoting survival and / or proliferation of T cells or NK cells in culture without adding IL-2, are provided. Furthermore, additional regulatory elements are provided, such as inhibitory RNA molecules.
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Description

[0001] Cross References to Related Applications

[0002] This application is a continuation-in-part of International Application No. PCT / US2018 / 020818, filed March 3, 2018; and claims the benefit of: U.S. Provisional Application No. 62 / 560,176, filed September 18, 2017; 2017 U.S. Provisional Application No. 62 / 564,253, filed September 27, 2017; U.S. Provisional Application No. 62 / 564,991, filed September 28, 2017; and U.S. Provisional Application No. 62 / 728,056, filed September 6, 2018 ; International Application No. PCT / US2018 / 020818 is a continuation-in-part of International Application No. PCT / US2017 / 023112 filed on March 19, 2017; International Application No. PCT / US2017 / 041277 filed on July 8, 2017 continuation-in-part of U.S. Application No. 15 / 462,855, filed March 19, 2017; and continuation-in-part of U.S. Application No. 15 / 644,778, filed July 8, 2017; and asserting Interest in: U.S. Provisional Application No. 62 / 467,039, filed March 3, 2017; U.S. Provisional Applicati...

Claims

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