METHODS AND COMPOSITIONS TO IMPROVE THE SAFETY AND EFFICACY OF CELLULAR THERAPIES

    公开(公告)号:US20220135678A1

    公开(公告)日:2022-05-05

    申请号:US17423894

    申请日:2020-01-18

    Abstract: Described herein are novel compositions and methods to improve the safety and efficacy of adoptive cellular therapies of cancer, infection, allergic, degenerative and immune disorders. The disclosure provides a) novel methods and compositions to reduce the accidental insertion of chimeric receptors into cancer cells; b) novel methods to measure the titer of viral vectors; c) novel compositions to generate antigen masking receptors and methods to use such receptors to protect normal cells from immunotherapeutic agents; d) novel compositions and methods to extend the life-span of allogeneic cells, including allogeneic CAR-T cells; e) novel compositions and methods to ameliorate the side-effects of cellular therapies and f) novel compositions of Synthetic Immune Receptors and Ab-TCRs with mutant TCRα constant chains.

    HIGHLY SENSITIVE AND SPECIFIC LUCIFERASE BASED REPORTER ASSAY FOR ANTIGEN DETECTION

    公开(公告)号:US20190107537A1

    公开(公告)日:2019-04-11

    申请号:US16089278

    申请日:2017-03-31

    Abstract: Provided herein are methods for detecting an antigen or for detecting expression of a chimeric antigen receptor (CAR). The methods include obtaining a sample from a subject, contacting the sample with a fusion protein comprising a reporter fused to a single chain antibody specific to the antigen or fused to an extracellular domain of an antigen targeted by the CAR or fused to Protein L and assaying the activity of the reporter, wherein presence of reporter activity or increase in reporter activity relative to a reference value is indicative of presence of the antigen or presence of the expression of the chimeric antigen receptor in the sample.

    NON-RADIOACTIVE CYTOTOXICITY ASSAYS

    公开(公告)号:US20220252606A1

    公开(公告)日:2022-08-11

    申请号:US17723284

    申请日:2022-04-18

    Abstract: Described herein are methods for assessing cytotoxicity of an agent. The methods include providing a target cell that has been engineered to express intracellularly a reporter that is not expressed endogenously by the target cell, exposing the target cell to an agent capable of modulating cytotoxicity and assaying the activity of the reporter, wherein a change in reporter activity relative to a reference value is indicative of the agent being able to modulate cytotoxicity of the target cell.

    NON-RADIOACTIVE CYTOTOXICITY ASSAYS
    18.
    发明申请

    公开(公告)号:US20190293656A1

    公开(公告)日:2019-09-26

    申请号:US16333980

    申请日:2017-09-19

    Abstract: Described herein are methods for assessing cytotoxicity of an agent. The methods include providing a target cell that has been engineered to express intracellularly a reporter that is not expressed endogenously by the target cell, exposing the target cell to an agent capable of modulating cytotoxicity and assaying the activity of the reporter, wherein a change in reporter activity relative to a reference value is indicative of the agent being able to modulate cytotoxicity of the target cell.

    CHIMERIC ANTIGEN RECEPTORS TARGETING CANCER
    20.
    发明申请

    公开(公告)号:US20190112380A1

    公开(公告)日:2019-04-18

    申请号:US16089106

    申请日:2017-03-29

    Abstract: Provided herein is a composition comprising, a cell, comprising nucleic acids encoding a chimeric antigen receptor (CAR) and one or more of signaling proteins selected from K13-vFLIP, MC159-vFLIP, cFLIP-L, cFLIP-p22, HTLV1-Tax and HTLV2-Tax, wherein the CAR comprises an a) extracellular antigen specific domain, b) a transmembrane domain and c) an intracellular signaling domain comprising an immunoreceptor tyrosine-based activation motif (ITAM); wherein c) is located at the C-terminus of the chimeric receptor. In some embodiments, the CAR further comprises one or more co-stimulatory domains. Also provided herein are methods for treating diseases using the compositions described herein.

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