Activation and expansion of T-cells using an engineered multivalent signaling platform
First Claim
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1. An engineered multivalent signaling platform (EMSP) for use in stimulating and/or activating T cells comprising an EMSP that expresses or displays on its surface one or more agents that ligate a cell surface moiety of at least a portion of T-cells and stimulates said T-cells.
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Abstract
The present invention relates generally to methods for activating and expanding cells, and more particularly, to a novel method to activate and/or stimulate cells using an engineered multivalent signaling platform. Compositions of cells activated and expanded by the methods herein are further provided.
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Citations
84 Claims
- 1. An engineered multivalent signaling platform (EMSP) for use in stimulating and/or activating T cells comprising an EMSP that expresses or displays on its surface one or more agents that ligate a cell surface moiety of at least a portion of T-cells and stimulates said T-cells.
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24. A method for activating or stimulating a population of T-cells by cell surface moiety ligation, comprising:
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a. providing a population of cells wherein at least a portion thereof comprises T-cells;
b. contacting said population of cells with an EMSP, said EMSP having on its surface one or more agents that ligate a cell surface moiety of at least a portion of said T-cells and activates or stimulates said T-cells. - View Dependent Claims (25, 26, 27, 28, 29, 30, 31, 78, 84)
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- 32. A method for maintaining T-cell repertoire comprising providing a population of cells having T-cells present therein, exposing said T-cells to an EMSP for a time sufficient to induce activation and subsequently expanding said T-cells.
- 35. A method for maintaining the viability of T-cells during culture, comprising contacting said T-cells with EMSP.
- 43. A method for decreasing apoptosis of a population of CD8+ T-cells, comprising stimulating said cells with EMSP, said EMSP having on its surface at least one primary stimulatory agent and at least one co-stimulatory agent.
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51. A method for expanding a population of T-cells by cell surface moiety ligation, comprising:
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a. providing a population of cells wherein at least a portion thereof comprises T-cells;
b. contacting said population of cells with an EMSP, said EMSP having on its surface one or more agents that ligate a cell surface moiety of at least a portion of said T-cells and activates or stimulates said T-cells; and
c. culturing said T-cells under conditions and time sufficient to induce cell division, wherein said contacting and/or said culturing occurs in the absence of exogenously added cytokines. - View Dependent Claims (52, 53, 54, 55, 56, 57, 58, 59, 71)
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60. A method for expanding a population of T-cells by cell surface moiety ligation, comprising:
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a. providing a population of cells wherein at least a portion thereof comprises T-cells;
b. contacting said population of cells with an EMSP, said EMSP having on its surface one or more agents that ligate a cell surface moiety of at least a portion of said T-cells and activates or stimulates said T-cells; and
c. culturing said T-cells under conditions and time sufficient to induce cell division. - View Dependent Claims (61, 62, 63, 64, 65, 66, 67, 68, 69, 70)
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72. A method of immunotherapy comprising administering an EMSP to a subject in need thereof, thereby stimulating a population of T-cells within the subject to expand.
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73. A method of enhancing reactivity to an antigen comprising administering an EMSP to a subject in need thereof concurrently, prior to or following inoculation of the subject with an antigen of interest, thereby stimulating a population of antigen specific T-cells within the subject to expand.
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74. A method for breaking immune tolerance comprising administering an EMSP to a subject either systemically or locally at a site of interest.
- 75. A method for increasing uptake of an exogenously added nucleic acid molecule in T-cells, comprising contacting said T-cells with an EMSP and contacting said T-cells with said nucleic acid molecule thereby, said contacting of EMSP with said T-cells rendering cells more amenable to uptake of nucleic acid.
- 79. A method of activating antigen specific T-cells, comprising contacting a population of T-cells an antigen and an EMSP under conditions and for time sufficient to induce activation of T-cells specific to said antigen.
Specification