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Universal Anti-cd22 chimeric antigen receptor engineered immune cells

An engineering and cellular technology, applied in the direction of blood/immune system cells, anti-animal/human immunoglobulin, anti-receptor/cell surface antigen/cell surface determinant immunoglobulin, etc., can solve uncertain, patient there is a problem etc.

Pending Publication Date: 2020-03-06
CELLECTIS SA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Also, this approach may be problematic or inconclusive in patients with altered immune systems

Method used

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  • Universal Anti-cd22 chimeric antigen receptor engineered immune cells
  • Universal Anti-cd22 chimeric antigen receptor engineered immune cells
  • Universal Anti-cd22 chimeric antigen receptor engineered immune cells

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[1019] Example 1: Proliferation of TCRα-inactivated cells expressing CD22 CAR.

[1020] A heterodimeric TALE nuclease targeting two 17 bp long sequences (called half-targets) in the T cell receptor alpha constant chain region (TRAC) gene separated by a 15 bp spacer was designed and produced. The repeat sequences of the half-TALE nucleases listed in Table 6 recognize each half-target.

[1021] Table 6: TAL nucleases targeting the TCRα gene

[1022]

[1023]

[1024] Each TALE nuclease construct was subcloned by restriction digest into a mammalian expression vector under the control of the T7 promoter. mRNA encoding the TALE nuclease that cleaves the TRAC genomic sequence was synthesized from a plasmid carrying the coding sequence downstream of the T7 promoter.

[1025]Purified T cells preactivated with anti-CD3 / CD28 coated magnetic beads for 72 hours were transfected with each of the 2 mRNAs encoding the two half TRAC_T01 TALE nucleases. 48 hours after transfection, di...

Embodiment 2

[1030] Example 2: CD22 CAR-T

[1031] Develop engineered CAR T cells targeting CD22 for the treatment of refractory, relapsed or aggressive ALL or CLL.

[1032] CD22 CAR:( figure 2 )

[1033] CD22 CARs were designed and prepared using different scFvs as constructs for m971 and m971 variants with reduced affinity for CD22 and high selectivity. m971 scfv derived from 971 antibody (Haso W 1 , Lee DW, Shah NN, Stetler-Stevenson M, Yuan CM, Pastan IH, Dimitrov DS, Morgan RA, FitzGerald DJ, Barrett DM, Wayne AS, Mackall CL, Orentas RJ. Anti-CD22-chimeric antigen receptors targeting B-cell precursor acute lymphoblastic leukemia. Blood. 2013 Feb 14; 121(7):1165-74. doi:10.1182 / blood-2012-06-438002. Epub 2012 Dec 14)

[1034] The construct has a CAR architecture with 4-1BB co-stimulatory domain, CD3ζ activation domain, CD8α transmembrane domain and hinge CD8α hinge (SEQ ID NO: 15) ( figure 2 ). This construct comprises the FcγRIIIα hinge corresponding to SEQ-ID N°14.

[1035] ...

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Abstract

The present invention relates to an engineered immune cell endowed with a new CD22 Chimeric Antigen Receptors (CD22 CAR) with a deletion in the TRAC gene that is able to redirect said immune cell specificity and reactivity toward selected tumor cells. The engineered immune cells endowed with such CARs are particularly suited for treating relapsed refractory CD22 expressing cancers.

Description

technical field [0001] The present invention relates generally to the field of immunotherapy, and more particularly to universal chimeric antigen receptor T cells specific for CD22 (UCART22) and methods for engineering said cells. Somatic T cells (UCART22) are engineered human primary immune cells containing at least one edited gene and a chimeric antigen receptor (CAR) specific for cluster of differentiation 22 (CD22) (CAR CD22), the edited The gene is preferably a gene encoding a TCR subunit or a CD52 gene. The invention further relates to the use of UCART22 as a refractory blood cell for relapse in patients who may or may not be the initial donor of the cells ("allogenic" or "autologous" CD22 CAR-engineered primary human immune cells) Application in the treatment of cancer. CD22 expressing cells according to the invention are particularly effective and safe for immunotherapy, especially against aggressive or recurrent cancers. Background technique [0002] Blood cancer...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/00A61K35/17C07K16/28C12N5/0783C07K19/00C07K14/47
CPCC07K16/2803C12N5/0638A61K2039/804C07K2317/622C07K2317/73C07K2319/03C07K2319/33C07K2319/74C07K14/7051C07K14/70517C07K14/70578C07K2319/02C07K14/47C07K19/00A61P35/00A61K39/464412A61K39/4611A61K39/4631A61K2239/28A61K39/464413A61P35/02C07K2317/34C07K2317/53A61K31/365C07K16/283A61K39/001113A61K39/39558A61K35/17
Inventor 朱莉安娜·史密斯菲利普·迪沙泰奥米里耶勒·德里耶
Owner CELLECTIS SA