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BCL11B overexpression to enhance human thymogenesis and t cell function

A cell and progenitor cell technology, applied in the field of BCL11B overexpression to enhance human thymus generation and T cell function, can solve the problems of limiting the efficacy of malignant tumors, lack, disease recurrence, etc.

Pending Publication Date: 2022-07-29
CHILDRENS HOSPITAL OF LOS ANGELES +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] Furthermore, engineered T cell immunotherapy has shown promising response rates in acute leukemias and lymphomas, but in many cases depletion or lack of persistence of infused T cells leads to disease relapse
Furthermore, poor function of infused T cells in the tumor microenvironment severely limits the efficacy of engineered T cells against solid malignancies

Method used

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  • BCL11B overexpression to enhance human thymogenesis and t cell function
  • BCL11B overexpression to enhance human thymogenesis and t cell function
  • BCL11B overexpression to enhance human thymogenesis and t cell function

Examples

Experimental program
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Effect test

Embodiment 1

[0125] BCL11B overexpression induces T cell differentiation of multilineage human hematopoietic stem and progenitor cells

[0126] This example illustrates the effect of overexpression of the transcription factor BCL11B in human HSPC and T cells in vitro.

[0127] HSPCs that migrate from the bone marrow (BM) and initiate T cell differentiation (thymopoiesis) in the human thymus can be described by the expression of the CD34 antigen and can constitute less than 1% of all thymocytes. The initial stage of thymopoiesis is marked by two processes: induction of T cell lineage gene expression (T cell lineage specialization), and loss of surrogate (non-T) cell lineage potential (T cell lineage commitment). The earliest thymic progenitor cells (CD34+CD7-CD1a-, Thy1; figure 1 ) has myeloid erythroid and panlymphoid (B, T and NK) potential. Successive phases of T cell lineage commitment are marked by the continuous upregulation of CD7 and CD1a and a progressive loss of surrogate cell l...

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Abstract

Disclosed herein are methods of treating a subject using T cell therapy. The methods include increasing expression of BCL11B in hematopoietic stem and progenitor cells (HSPCs), pluripotent stem cells, or mature T cells to form modified cells and administering a therapeutically effective amount of the modified cells to a subject for T cell therapy. The expression of BCL11B in HSPC, pluripotent stem cells, or mature T cells increases the production and / or proliferation of T cells from HSPC and / or pluripotent stem cells, and / or increases the proliferation of T cells.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS [0002] This application claims the benefit of US Provisional Application No. 62 / 865,835, filed June 24, 2019, the entire contents of which are incorporated herein by reference. [0003] Thanks for government support [0004] This invention was made with government support under K12-HD052954 awarded by the National Institutes of Health. The government has certain rights in the invention. technical field [0005] This relates to methods of generating T cell populations for T cell therapy, and to treating a subject using T cell therapy. Background technique [0006] More than 8,000 children and adults in the United States receive allogeneic hematopoietic stem cell transplantation (HSCT) each year, a treatment for a variety of benign and malignant blood disorders and genetic disorders. However, a major ongoing challenge is the significant morbidity and mortality of serious infections and the recurrence of malignant disease asso...

Claims

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Application Information

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IPC IPC(8): A61K39/00A61K35/17A61P37/00A61P35/00
CPCA61K35/14A61P37/00A61K39/4621A61K39/4632A61K39/46433A61K39/464402A61K39/4631A61K39/4611A61K39/46434A61K35/17A61K35/28A61K35/545A61K38/177A61K38/1774
Inventor 钦腾·帕雷克盖伊·克鲁克斯克里斯多夫·西特阿梅莉·蒙特尔-哈根
Owner CHILDRENS HOSPITAL OF LOS ANGELES