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In vitro artificial lymph node method for sensitization and expansion of t cells for therapy and epitope mapping

A cell and cell group technology, applied in biochemical equipment and methods, animal cells, antibody medical components, etc., can solve the problems of loss of specific function of cell death antigens, insufficient amplification level, etc.

Inactive Publication Date: 2018-01-02
布莱恩 J 赫尔尼奇
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there are many technical problems in practice, including insufficient levels of expansion, premature activation-induced cell death (apoptosis), or loss of antigen specificity and / or function
[0007] Part of the problem is the inability to replicate in vitro the environment in which antigen-specific T cell expansion occurs in lymph nodes in vivo

Method used

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  • In vitro artificial lymph node method for sensitization and expansion of t cells for therapy and epitope mapping
  • In vitro artificial lymph node method for sensitization and expansion of t cells for therapy and epitope mapping
  • In vitro artificial lymph node method for sensitization and expansion of t cells for therapy and epitope mapping

Examples

Experimental program
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Embodiment 1

[0240] Example 1: Anti-HER2CD4 in breast cancer patients inoculated with type I dendritic cells + Restoration of Th1 responses

[0241] The following study was designed to explore the role of helper type 1 polarized dendritic cell ("DC1") seeding.

[0242] Type I dendritic cell vaccination with HER2 with residual disease after neoadjuvant therapy + IBC patients

[0243] Four HER2 patients with residual disease after neoadjuvant therapy + IBC patients receive adjuvant HER2-pulsed type I dendritic cell vaccine. The Th1 immune response of each patient was determined before type I dendritic cell inoculation, 3 months after dendritic cell inoculation and 6 months after inoculation, and from six HER2 II peptides (SEQ ID NO: 1-6 ) pulsed patient PBMC production by measuring IFNγ production by ELISPOT as described above. Autologous type I dendritic cell vaccines were prepared as previously described. (1) overall anti-HER2 response rate (response rate >1 peptide), (2) number ...

Embodiment 2

[0251] In vitro expansion of embodiment 2-HER2-specific Th1 cells

[0252] The following study was designed to interrogate the role of adoptive T cell transfer in restoring anti-HER2Thl immunity. T cell expansion to levels required for adoptive therapy and epitope mapping studies while maintaining antigen specificity and cellular function.

[0253] Briefly, in vitro, HER2-specific Th1 cells were generated by co-culture with HER2 peptide-pulsed type I dendritic cells and expanded using IL-2 alone or IL-2, IL-7, and IL-15 . Th1 cells were subsequently expanded by repeated HER2-peptide pulses of type I dendritic cell co-culture or by anti-CD3 / CD28 stimulation. The expansion factor was defined as: (the number of T cells after expansion / the number of T cells before expansion); the specificity of antigen-specific IIγ production was determined by ELISA.

[0254] As shown in this paper, CD4 + Repeated co-culture of T cells with HER2 peptide pulsed with type I dendritic cells stimu...

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Abstract

A method of creating a microenvironment for culture expansion of T cells. The expanded T cells can be used for a variety of therapeutic and research purposes.

Description

[0001] This application claims priority to and benefit from U.S. Provisional Patent Application No. 62 / 138,969, filed March 26, 2015. technical field [0002] This example relates to methods of sensitization and expansion of T cells for therapy and epitope mapping in artificial lymph nodes in vitro and diagnostic monitoring methods, therapeutic methods and tools based thereon. Background technique [0003] The lifetime risk of developing breast cancer is almost one in eight. The erb-B2 oncogene (HER-2 / neu) is a molecular driver overexpressed in a large number of breast, ovarian, gastroesophageal, lung, pancreatic, prostate and other solid tumors. HER2 overexpression (“HER2 pos ”) one is a driver molecule in several tumor types comprising approximately 20-25% of breast cancers (Meric, F., et al., J. AmColl. Surg. 194:488-501 (2002)), which is associated with invasion Sexual clinical course, resistance to chemotherapy, and overall poor prognosis in breast cancer ("BC"). See ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/00A61K39/00C12N5/0783C12N5/0784
CPCC12N2501/11C12N2502/1121A61K2039/5158C12N5/0636A61P35/00A61K39/0011A61K2039/5154A61K2039/55533G01N33/574
Inventor 布莱恩·J·赫尔尼奇莉亚·洛温菲尔德
Owner 布莱恩 J 赫尔尼奇
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