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Cancer Research
同源小鼠 B 细胞淋巴瘤模型对 CD19 轿车 T 细胞的临床前评价
同源小鼠 B 细胞淋巴瘤模型对 CD19 轿车 T 细胞的临床前评价
JoVE Journal
Cancer Research
This content is Free Access.
JoVE Journal Cancer Research
A Syngeneic Mouse B-Cell Lymphoma Model for Pre-Clinical Evaluation of CD19 CAR T Cells

同源小鼠 B 细胞淋巴瘤模型对 CD19 轿车 T 细胞的临床前评价

Full Text
15,677 Views
12:16 min
October 16, 2018

DOI: 10.3791/58492-v

Gray Kueberuwa1, Weiming Zheng1, Milena Kalaitsidou1, David E. Gilham1,2, Robert E. Hawkins1

1Manchester Cancer Research Centre Building, Department Cancer Sciences,University of Manchester, 2Celyad

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Please note that some of the translations on this page are AI generated. Click here for the English version.

Overview

This article presents a protocol for producing murine CD19 CAR T cells through retroviral transduction. It explores their application as a therapy against established syngeneic A20 B-cell lymphoma in BALB/c mice, with or without lymphodepleting pre-conditioning.

Key Study Components

Area of Science

  • Immunotherapy
  • Oncology
  • Cellular Biology

Background

  • CAR T-cell therapy is a promising approach in cancer treatment.
  • Understanding the interaction between CAR T-cells and endogenous immune cells is crucial.
  • The study focuses on comparing lympho-replete and lympho-depleted settings.
  • Insights gained may be applicable to solid tumors and other therapeutic targets.

Purpose of Study

  • To develop a protocol for generating CD19 CAR T cells.
  • To evaluate the efficacy of these cells in treating lymphoma.
  • To investigate the role of the immune environment in therapy outcomes.

Methods Used

  • Preparation of media and cells as per the outlined protocol.
  • Seeding of platinum E-Cells in culture dishes.
  • Incubation of cells under controlled conditions.
  • Assessment of CAR T-cell functionality in different immune settings.

Main Results

  • Successful production of murine CD19 CAR T cells.
  • Demonstrated differences in therapeutic efficacy based on immune conditioning.
  • Insights into the role of endogenous immune cells in therapy response.
  • Potential implications for broader applications in oncology.

Conclusions

  • The protocol provides a valuable tool for CAR T-cell research.
  • Findings contribute to understanding CAR T-cell interactions in vivo.
  • Future studies may expand on these findings to improve cancer therapies.

Frequently Asked Questions

What is CAR T-cell therapy?
CAR T-cell therapy involves modifying a patient's T cells to better recognize and attack cancer cells.
How does lymphodepletion affect CAR T-cell therapy?
Lymphodepletion can enhance the efficacy of CAR T-cells by reducing competition from endogenous immune cells.
What are the implications of this study?
The study's findings may inform future CAR T-cell therapies and their application in treating solid tumors.
What model organism is used in this research?
BALB/c mice are used as the model organism for testing the CAR T-cell therapy.
What is the significance of using syngeneic A20 B-cell lymphoma?
Using syngeneic A20 B-cell lymphoma allows for a more accurate assessment of the immune response to the therapy.
What are the next steps for this research?
Future research may focus on optimizing CAR T-cell designs and exploring their use against other cancer types.

在这里, 我们提出了一个协议, 用于生产和临床前测试小鼠 CD19 汽车 T 细胞的逆转录病毒转导和利用, 作为一种治疗同源 A20 B 细胞淋巴瘤在 BALB/c 鼠有或没有 lymphodepleting预调理。

这种方法可以帮助我们回答汽车T细胞免疫治疗领域的关键问题,如汽车T细胞的基因改造和其他免疫疗法的组合。这种技术的主要优点是允许比较淋巴精和淋巴耗尽设置。这使我们能够看到内源性免疫细胞在疾病进展中的作用,以及它们与治疗性 CAR T 细胞的相互作用。 这项技术对实体肿瘤的诊断具有10个作用,因为该模型中学到的教训可以直接转化为糖果的家与其他靶点,如CEA。开始此过程。首先,准备文本协议中概述的所有需要的媒体和单元格。第一天在完整的DMEM到15平方厘米的文化菜肴。种子750万铂银细胞在这些菜肴和孵化过夜在37

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癌症研究 问题 140 汽车 t 细胞 卡车 收养 t 细胞疗法 同源小鼠模型 A20 免疫治疗 IL-12 预调理 CD19 淋巴瘤

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