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EXPANSION OF NON-HAEMATOPOIETIC TISSUE-RESIDENT [gamma][delta]T CELLS AND USES OF THESE CELLS

A technology of hematopoietic tissue and hematopoietic cells, which can be used in blood/immune system cells, tissue culture, animal cells, etc., and can solve problems such as low efficiency and expansion of γδT cells

Pending Publication Date: 2018-08-31
CANCER RES TECH LTD +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

A major concern regarding the limited clinical efficacy of cells is their propensity to become irreversibly exhausted by chronic antigen exposure
A second major concern is their apparent inefficiency in homing to solid tumors and the tissues containing these tumors (23)
To date, no method has been described to significantly expand γδ T cells residing in nonhematopoietic tissues

Method used

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  • EXPANSION OF NON-HAEMATOPOIETIC TISSUE-RESIDENT [gamma][delta]T CELLS AND USES OF THESE CELLS
  • EXPANSION OF NON-HAEMATOPOIETIC TISSUE-RESIDENT [gamma][delta]T CELLS AND USES OF THESE CELLS
  • EXPANSION OF NON-HAEMATOPOIETIC TISSUE-RESIDENT [gamma][delta]T CELLS AND USES OF THESE CELLS

Examples

Experimental program
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Embodiment Construction

[0087] Gamma delta T cells (gamma delta T cells) represent a small subset of T cells expressing the distinct, defining T cell receptors (TCRs) on their surface. The TCR consists of a γ (gamma) and a δ (delta) chain.

[0088] There are two major subtypes of human γδ T cells: one predominates in peripheral blood and the other in nonhematopoietic tissues.

[0089] The nonhematopoietic tissue localization of the second subtype of human γδ T cells makes it more difficult to sample, and there is no established means of culturing the cells. To meet this need, the present invention relates to a method of expanding non-hematopoietic tissue resident γδ T cells (alternatively referred to herein as non-hematopoietic native γδ T cells). These γδ T cells typically reside in nonhematopoietic tissues. As described herein, the non-hematopoietic tissue-resident γδ T cells used may be derived from or obtained from non-hematopoietic tissue. Nonhematopoietic tissues may contain nonhematopoietic...

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Abstract

This invention relates to the expansion of non-haematopoietic tissue-resident [gamma][delta]T cells in vitro by culturing lymphocytes obtained from non-haematopoietic tissue of humans or non-human animals in the presence of interleukin-2 (IL-2) and / or interleukin-15 (IL-15) and the absence of TCR activation or co-stimulation signals, without any direct contact with stromal or epithelial cells. Methods of non-haematopoietic tissue-resident [gamma][delta]T cell expansion are provided, as well as populations of non-haematopoietic tissue-resident [gamma][delta]T cells and uses thereof.

Description

technical field [0001] The present invention relates to a method for ex vivo expansion of non-hematopoietic tissue-resident γδ T cells. The term "non-hematopoietic tissue resident γδ T cells" refers to a subset of T lymphocytes that reside in non-hematopoietic tissues other than lymphoid organs and blood. Such cells include non-Vδ2 cells, eg, Vδ1, Vδ3 and Vδ5 cells. The invention also relates to the use of these cells in adoptive T cell therapy and in chimeric antigen receptor therapy, as well as their use in methods of screening for checkpoint modulators. The present invention also relates to cells produced as a result of ex vivo expansion of non-hematopoietic tissue-resident γδ T cells. Background technique [0002] Increasing interest in T cell immunotherapy for cancer has focused on the apparent functional potential of CD8+(1-4) and CD4+αβ(5,6) T cell subsets to recognize cancer cells and mediate host protection Capacity, especially when derepressed by clinically medi...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N5/0783
CPCC12N2501/2302C12N2501/2315C12N5/0638A61P31/12A61P31/18A61P31/22A61P35/00A61K39/4611A61K39/4644G01N33/505
Inventor 阿德里安·海戴奥利弗·努斯鲍莫理查德·伍尔夫
Owner CANCER RES TECH LTD