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Cell composition comprising antigen-specific cells for adoptive therapy

A composition and specific technology, applied in the direction of genetically modified cells, medical raw materials derived from mammals, drug combinations, etc., can solve the problem of limited flexibility of therapy

Pending Publication Date: 2020-09-04
耐克西缪恩有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Further, these therapies often have limited flexibility due to the engineered single target

Method used

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  • Cell composition comprising antigen-specific cells for adoptive therapy
  • Cell composition comprising antigen-specific cells for adoptive therapy
  • Cell composition comprising antigen-specific cells for adoptive therapy

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Embodiment

[0139] Antigen-specific T cells are enriched and expanded from donor cells isolated by leukapheresis. CD4+ cells were removed from the cells by negative selection using CD4 microbeads. Antigen-specific T cells were enriched in the resulting cells by co-incubating the resulting cells with paramagnetic nanoparticles (dextran-coated iron oxide nanoparticles, approximately 80 to 200 nm in diameter). The nanoparticles have a dimeric HLA ligand (presenting the target peptide antigen) and an agonistic anti-CD28 monoclonal antibody conjugated to the surface. Dimeric HLA ligands contain two HLA-A2 domains containing the peptide-binding groove, each fused to an arm of the Ig hinge region. Combine dimeric HLA-Ig with β 2 Microglobulin co-expression. Ligands and aAPC constructs are disclosed in WO 2016 / 044530 and WO 2016 / 105542 (both of which are herein incorporated by reference in their entirety).

[0140] Cells were incubated in the presence of paramagnetic aAPCs and then in the pre...

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Abstract

The present invention provides an isolated cell composition suitable for adoptive immunotherapy, as well as methods of manufacturing the cell compositions and methods of treatment with the cell compositions. The composition comprises, in a pharmaceutically acceptable carrier, at least about 106 CD8+ T cells specific for target peptide antigen(s). In various embodiments, the composition is predominately CD8+ T cells, and at least about 20% of T cells in the composition exhibit a central or effector memory phenotype, providing for a robust and durable adoptive therapy from a natural T cell repertoire that has undergone natural selection.

Description

[0001] priority [0002] This application claims the benefit of U.S. Provisional Application No. 62 / 561,044 (filed: September 20, 2017) and U.S. Provisional Application No. 62 / 656,679 (filed: April 12, 2018), each of which is incorporated by reference method is incorporated into this article as a whole. Background technique [0003] Adoptive immunotherapy, such as donor lymphocyte infusion, is used to treat leukemia relapse after hematopoietic stem cell transplantation (HSCT) to enhance the graft-versus-leukemia (GVL) effect. These pathways often take months to take effect and require very large cell doses, which pose a significant risk of graft-versus-host disease (GVHD). See McLaughlin L et al., Adoptive T-cell therapies for refractory / relapsed leukemia and lymphoma; current strategies and recent advances .Ther.Adv.Hematol. 2015 Vol.6(6)295-307. [0004] With current treatment options, outcomes for leukemia patients relapsed after eg HSCT are bleak. While adoptive cell...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/00C12N13/00B03C1/28
CPCB03C1/01C12N13/00B03C2201/18B03C2201/26A61K2039/5158C12N2501/51C12N2502/99A61K2039/876A61K39/001191C12N5/0636A61P35/02C12N2501/21C12N2501/2301C12N2501/2321C12N2501/2304C12N2501/2302C12N2501/24C12N2501/2306C12N2527/00C12N2501/231C12N2502/1114A61K35/17
Inventor 马赛厄斯·厄可克丽丝蒂·琼斯金素贞劳伦·苏亚雷斯肯·卡特斯科特·卡莫丹·贝德纳里克
Owner 耐克西缪恩有限公司