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Immunologically discernible cell surface variants for use in cell therapy

A cell and surface protein technology, applied in genetically modified cells, receptors/cell surface antigens/cell surface determinants, cells modified by introducing foreign genetic material, etc., can solve the problems of on-target and off-target effects

Pending Publication Date: 2019-08-30
UNIVERSITY OF BASEL
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Transfer of CAR-T cells can lead to severe on-target and off-target effects (cytokine release syndrome), and transfer of allogeneic T cells can lead to graft-versus-host disease (GvHD)

Method used

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  • Immunologically discernible cell surface variants for use in cell therapy
  • Immunologically discernible cell surface variants for use in cell therapy
  • Immunologically discernible cell surface variants for use in cell therapy

Examples

Experimental program
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Embodiment Construction

[0221] The following descriptions can be found in EP16196860.7, EP16196858.1 and PCT / EP2017 / 059799: Efficient plasmid-based gene ablation in primary T cells, targeted introduction of point mutations in primary T cells, by Enrichment of HDR-edited cells by monitoring isotype switching of alternative cell surface markers, and gene correction of mouse scurfy cells.

[0222] General considerations for designing engineered mutations (allele engineering):

[0223] Allelic engineering of genes by introducing site-directed small mutations (perhaps single nucleotide or single amino acid mutations) with the aim of altering the specific binding of the ligand and allowing the binding of a second specific ligand can be used as a general principle for therapeutic use. Mutations are designed in such a way that the functionality of the engineered protein is preserved as much as possible. Immunogenicity needs to be altered to enable the generation of specific binding ligands, such as monoclo...

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PUM

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Abstract

The invention relates to a mammalian cell, particularly a human cell, expressing a first isoform of a surface protein, wherein the first isoform is functionally indistinguishable, but immunologicallydistinguishable from a second isoform, for use in a medical treatment of a patient having cells expressing the second isoform form of the surface protein. The invention further relates to an agent selected from 1) a compound comprising, or consisting of, an antibody or antibody-like molecule and 2) an immune effector cell bearing an antibody-like molecule or an immune effector cell bearing a chimeric antigen receptor, for use in a method of treatment of a medical condition, wherein the agent is specifically reactive to either a first or a second isoform of a surface protein, wherein the firstisoform is functionally indistinguishable, but immunologically distinguishable from the second isoform, and wherein the agent is administered to ablate a cell bearing the isoform that the agent is reactive to.

Description

technical field [0001] The present invention relates to the use of cells with mutated but functional cell surface proteins in medical applications where selective depletion or enrichment of cell populations is desired. Mutant but functional cell surface proteins can be introduced into cells by gene editing methods (including homology-directed repair of DNA double-strand breaks, especially during CRISPR / Cas gene editing) or by using base editors. The invention further relates to reagents and methods for selectively depleting edited cells in vivo. Background technique [0002] Cell therapy is a very effective treatment option, but is often associated with serious adverse side effects. Transgenic and / or genetic engineering of metastatic cells can cause malignant transformation. The transfer of CAR-T cells can lead to severe on-target and off-target effects (cytokine release syndrome), and the transfer of allogeneic T cells can lead to graft-versus-host disease (GvHD). The su...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N5/10A61K35/12C07K14/705C12N15/90A61P37/06
CPCA61K35/00A61K35/12C12N2510/00A61P35/02C07K2319/03C12N15/102C12N2310/20C12N9/22C07K14/705C12N15/902A61K39/4644A61K2239/38A61K39/4611C07K14/70589C07K2317/31A61P7/06C07K16/2896C07K2319/20A61P37/06C07K16/289C12N15/907C12N5/0636C07K14/70596C07K2317/622C12N15/113C12N5/00A61K35/17C12N9/78C07K14/7051C07K16/2803A61K39/4631A61P35/00
Inventor L·杰克M·科内特L·博多里·施韦德T·施韦德R·莱波雷R·马特尔·马罗内M·雷彻
Owner UNIVERSITY OF BASEL
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