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Car-cd30 t cells for treatment of cd30+ tumors

A 1. CD30, cell technology, applied in the field of CAR-CD30 T cells, can solve the problem that the clinical benefit is not the best

Pending Publication Date: 2021-01-22
OSPEDALE PEDIATRICO BAMBINO GESU
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] Immunotherapy approaches targeting CD30 via CARs have demonstrated value in preclinical models (8, 9) and in two separate independent clinical trials (10, 11), although the clinical benefit is not optimal

Method used

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  • Car-cd30 t cells for treatment of cd30+ tumors
  • Car-cd30 t cells for treatment of cd30+ tumors
  • Car-cd30 t cells for treatment of cd30+ tumors

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0226] Example 1: In vitro and in vivo design and research of CAR-CD30 according to the present invention

[0227] Materials and methods

[0228] Design of CAR-CD30 plasmid (construct)

[0229] Two clinical-grade "third" generation retroviral vectors, SFG, have been designed carrying an anti-CD30 single-chain variable fragment (scFv) derived from an IgG(AC10)-like murine antibody, codon-optimized human CD8 hinge - the expression cassette of the codon-optimized signaling domain of the transmembrane domain linked to the two co-stimulatory domains CD28, 4-1BB (CD137) or OX40 and CD3-zeta ( figure 1 A). The CD30-specific single-chain variable fragment (scFv) is a fusion protein of 111 amino acids (aa) of the variable region of the immunoglobulin light chain (VL), consisting of an 8-amino acid flexible region (27) (short linker peptide ) is linked to 117 aa of the immunoglobulin heavy chain (VH). In particular, the scFv AC10 was cloned in the same reading frame as a codon-opti...

Embodiment 2

[0296] Example 2: Tumor regulation of memory and exhaustion in CAR.CD30 T cells (28.OX40.ζ T cells and 28.4-1BB.ζ T cells) according to the invention

[0297] Materials and methods

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Abstract

The present invention concerns a third generation of CAR-CD30 T cells for treatment of CD30+ Tumors such as lymphoid malignancies, leukemia, solid tumors.

Description

technical field [0001] The present invention relates to CAR-CD30 T cells for treating CD30+ tumors. In particular, the present invention relates to third-generation CAR-CD30 T cells for treating CD30+ tumors (such as lymphoid malignancies, leukemia, solid tumors). Background technique [0002] It is well known that the prognosis of most chemotherapy-refractory or multiple relapsed non-Hodgkin lymphoma (NHL) or Hodgkin lymphoma (HL) patients remains poor (1). Although allogeneic HSCT (allo-HSCT) offers the potential to cure patients with various lymphoma subtypes, transplant-related mortality remains high and long-term sequelae, including chronic graft-versus-host disease (GVHD), pose a significant Quality of life is substantially negatively affected (2). [0003] PD-1 blockade appears to be very effective in relapsed lymphoma after allo-HSCT, but is often accompanied by a rapid onset of severe and refractory GVHD (3). CAR-T cells are emerging as a novel treatment approach...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/00
CPCC07K14/7051C07K14/70517C07K14/70521C07K16/2878C07K2317/622C07K2319/03C07K2319/33A61K2239/28C12N5/0636A61K39/464417A61K39/4611A61K2239/38A61K2239/48A61K39/4631A61K2239/31A61P35/00A61K38/00C07K14/70578C07K2319/02C12N2501/2307C12N2501/2315
Inventor 比亚吉奥·德·安吉丽斯康塞塔·奎塔雷利伊格纳齐奥·卡鲁阿纳佛朗哥·洛卡特利
Owner OSPEDALE PEDIATRICO BAMBINO GESU
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