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Methods of transducing and expanding immune cells and uses thereof

A cell and transduction technology, applied in the direction of blood/immune system cells, chemical instruments and methods, biochemical equipment and methods, etc., can solve the problems of modification and expansion of immune cells, such as difficulty, high cost, pollution, etc.

Pending Publication Date: 2019-09-13
埃克苏马生物技术公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Previous methods for modifying and expanding immune cells for cell-based adoptive immunotherapy can be difficult, labor-intensive, costly, and include multiple steps where contamination can occur
Furthermore, such an approach may be limited in its efficiency to assist the many subjects that would benefit from it, as it may require specific techniques or equipment such that its deployment may be limited to specialized in vitro manufacturing facilities

Method used

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  • Methods of transducing and expanding immune cells and uses thereof
  • Methods of transducing and expanding immune cells and uses thereof
  • Methods of transducing and expanding immune cells and uses thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment approach 1A1

[0191] Embodiment 1A1. A method for transducing T cells and / or NK cells from isolated blood comprising:

[0192] a) enriching peripheral blood mononuclear cells (PBMCs) to separate PBMCs comprising T cells and / or NK cells from the isolated blood;

[0193] b) activating T cells and / or NK cells of isolated PBMCs and not enriching T cells and / or NK cells from other PBMCs under effective conditions in a closed system comprising an effective amount of an anti-CD3 antibody in solution; and

[0194] c) transducing activated T cells and / or NK cells with non-replication competent recombinant retroviral particles under effective conditions, thereby generating genetically modified T cells and / or NK cells, wherein activation and transduction are performed in Performed in the same closed system without washing the cells between activation and transduction.

Embodiment approach 1

[0195] Embodiment 1A2. The method of embodiment 1A1, further comprising expanding the genetically modified T cells and / or NK cells in the cell expansion medium to a volume of more than 150 ml and an expansion completion selection criterion selected from: Lactate concentration greater than 10 mM, at least 5-fold expansion of T cells and / or NK cells, and at least 10 days in cell expansion medium.

Embodiment approach 1A3

[0196] Embodiment 1A3. The method of embodiment 1A1, wherein the amplification is performed in the same chamber of the same closed system as the activation and transduction.

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Abstract

The present disclosure provides methods for genetically modifying and expanding immune cells ex vivo, especially for use in cell-based adoptive immunotherapy. As such, method embodiments are providedfor transducing immune cells (e.g. T cells and / or NK cells) that include a step of activating the cells and genetically modifying the activated cells, for example by transducing the cells with recombinant retroviral particles, such as lentiviral particles. Genetically modified cells produced by these methods are also provided. Such methods are typically performed within a closed system, and in illustrative embodiments within a single chamber of a closed system. The methods typically include expanding the genetically modified immune cells in cell expansion media within the closed system, in illustrative embodiments within the single chamber of the closed system. As such, provided herein in illustrative embodiments, are fed-batch, single-reactor method systems.

Description

[0001] Cross References to Related Applications [0002] This application claims U.S. Provisional Application No. 62 / 447,894, filed January 18, 2017, U.S. Provisional Application No. 62 / 447,913, filed January 19, 2017, and U.S. Provisional Application No. 62 / 4, filed March 3, 2017 467,062 in equity. These applications cited in this paragraph are hereby incorporated by reference in their entirety. technical field [0003] The present disclosure relates to methods for transducing and expanding immune cells in vitro. Background technique [0004] In adoptive cell therapy, immune cells isolated from a patient can be genetically modified in vitro to express synthetic proteins that enable the cells to perform new therapeutic functions after their serial transfer back into the patient. The modified cells are typically expanded in vitro to provide sufficient numbers of cells to perform therapeutic function prior to transferring the cells back into the patient. Previous methods fo...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N5/0783
CPCC12N5/0636C12N5/0638C12N5/0646C12N2500/32C12N2501/2302C12N2501/2307C12N2501/51C12N2501/515C12N2510/00C07K2319/03C07K14/7051A61K39/4611A61K39/464411A61K39/4631
Inventor 格雷戈里·伊恩·弗罗斯特詹姆斯·约瑟夫·奥努弗
Owner 埃克苏马生物技术公司