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Combinations for t-cell immunotherapy and uses thereof

A technology of cells and uses, applied in the field of combinations and uses thereof for T cell immunotherapy

Active Publication Date: 2022-03-22
MANYSMART THERAPEUTICS INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, CAR technology is still limited by the fact that the source of T cells must be the patient himself, and CAR must first be transduced into T cells to form CAR T cells. The CAR T cells need a long time to proliferate before autologous transplantation. into the patient

Method used

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  • Combinations for t-cell immunotherapy and uses thereof
  • Combinations for t-cell immunotherapy and uses thereof
  • Combinations for t-cell immunotherapy and uses thereof

Examples

Experimental program
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example

[0071] The present invention is illustrated in further detail by referring to the following experimental examples. The examples are provided for purposes of illustration only and are not intended to be limiting unless otherwise stated. Accordingly, the invention should in no way be construed as limited to the following examples, but rather should be understood to cover any and all variations which become apparent as a result of the teachings provided herein.

example 1

[0073] Isolation and identification of γ9δ2 T cells

[0074] According to the objective of the present invention, it is first necessary to cultivate effector memory type γ9δ2 T cells capable of killing blood cancer cells. γ9δ2 T cells can be identified by flow cytometry using anti-CD3 antibody, anti-γ9 antibody and anti-δ2 antibody at the same time. One of the characteristics of effector memory γ9δ2 T cells is that they do not have CD27 and CD45RA molecules on the cell surface.

[0075] According to the literature published by Kondo et al., Cytotherapy, 10, 842-56 (2008), peripheral blood mononuclear cells were treated with interleukin-2 (IL-2, 1000 U / ml) and zoledronic acid (Zoledronic acid) ) (1 μM / ml) stimulated culture for 14 days, the proportion of δ2 cells in the cultured cells was analyzed by flow cytometry using anti-δ2 antibody. Then, the δ2 ​​cells were purified with MiltenyiBiotec's reagent set (TCRγ / δ+T cell isolation Kit / human), and the purified cells were analy...

example 2

[0078] γ9δ2 T cells and In vitro test of (BiTE) toxicity against blood cancer cells

[0079] This experiment was carried out with reference to the method disclosed by Sheehy et al. (J Immunol Methods, 249, 99-110 (2001)).

[0080] In this experiment, Raji, VAL and Daudi blood cancer cells that express CD19 molecules are used as target cells, among which Raji and Daudi cell lines are CD19 + Burkett lymphoma cells, and the VAL cell line is CD19 + ALL cells. RPMI-8226 cell line is CD19 - Multiple myeloma cells.

[0081] Raji, RPMI-8226, VAL and Daudi blood cancer cell lines were stained with 5(6)-carboxyfluorescein diacetate succinimidyl ester (CFSE) After staining, inoculate in each well of the culture plate (5×10 4 each / hole). The γ9δ2 T cells obtained from Example 1 (1×10 6 each / hole) and (15ng / hole) were added independently or jointly to each hole containing different cells, and after 6 hours of culture, the CFSE+ cells were analyzed by flow cytometry to analyze th...

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Abstract

The present invention provides a combination comprising a bispecific T cell activating antigen binding molecule and an effector memory γ9δ2 T cell. Also disclosed are methods of using the combinations to treat diseases such as cancer and infectious diseases.

Description

technical field [0001] The present invention relates to combinations of T cells and bispecific T cell activating antigen binding molecules and methods of using said combinations in immunotherapy, eg in the treatment of cancer. Background technique [0002] In the clinic, to treat disease, it is often necessary to selectively destroy individual cells or specific cell types within an individual. Taking cancer therapy as an example, its main goal is to specifically destroy tumor cells while sparing healthy cells and tissues. [0003] To achieve this goal, a variety of bispecific antibodies that can be used in T cell-mediated immunotherapy have been developed. Bispecific T cell engager (Bispecific T Cell Engager (BiTE)) is a well-studied and clinically shown its prospects (Holliger et al., Protein Engineering (Prot Eng), 9, 299-305 (1996), Kipriyanov et al., J Mol Biol, 293, 41-66 (1999), Nagorsen and Exp Cell Res, 317, 1255-1260 (2011) and Sheridan, Nature Biotechnology, 34...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12N5/0783A61K35/17A61K39/395A61P35/00A61P35/02
CPCA61P35/02A61P35/00A61K35/17A61K39/395A61K2300/00C07K2317/31A61K39/3955
Inventor 黄馨仪
Owner MANYSMART THERAPEUTICS INC
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