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Related Concept Videos

T Cell Activation and Clonal Selection01:22

T Cell Activation and Clonal Selection

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T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
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Cytotoxic T Cells-mediated Immune Response01:27

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Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
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T Cell Types and Functions01:24

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When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
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Related Experiment Video

Updated: Dec 13, 2025

In Vitro Tumor Cell Rechallenge For Predictive Evaluation of Chimeric Antigen Receptor T Cell Antitumor Function
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Gamma-Delta CAR-T Cells Show CAR-Directed and Independent Activity Against Leukemia.

Meir Rozenbaum1,2,3, Amilia Meir3, Yarden Aharony3

  • 1Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.

Frontiers in Immunology
|July 28, 2020
PubMed
Summary

Donor-derived gamma delta T cells (γδT cells) offer a promising alternative to autologous CAR-T therapy for B-cell malignancies. This study demonstrates a feasible production process for potent γδCAR-T cells effective against CD19+ and CD19-negative leukemia.

Keywords:
B cell malignancieschimeric antigen receptorgamma-delta T cellsimmuno oncologyleukemia

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Area of Science:

  • Immunology
  • Oncology
  • Cell Therapy

Background:

  • Autologous CD19-directed chimeric antigen receptor (CAR)-T cells are effective in B-cell malignancies but face manufacturing challenges and antigen loss-related relapse.
  • Donor-derived gamma delta T cells (γδT cells) present an allogeneic, off-the-shelf alternative with inherent anti-tumor activity.

Purpose of the Study:

  • To develop and evaluate a novel production process for allogeneic γδT cells engineered to target CD19 (γδCAR-T cells).
  • To assess the efficacy of γδCAR-T cells against CD19-positive and CD19-negative leukemia models.

Main Methods:

  • A 14-day production protocol was established using peripheral blood mononuclear cells to expand and transduce γδT cells.
  • Transduction efficiency, cell purity, and in vitro/in vivo anti-leukemic activity were evaluated.
  • Efficacy was assessed in CD19+ cell lines and an NSG mouse model, including studies with zoledronate priming.

Main Results:

  • The process yielded highly pure (>98% CD3+, >99% γδTCR+) γδT cells with significant expansion (median 185-fold).
  • γδCAR-T cell transduction efficiency was comparable to standard CAR-T cells.
  • Effective in vitro and in vivo targeting of CD19+ leukemia was observed, with enhanced tumor reduction upon multiple injections and zoledronate priming.
  • Notably, γδCAR-T cells demonstrated efficacy against CD19 antigen-negative leukemia, an effect amplified by zoledronate priming.

Conclusions:

  • A feasible and efficient method for producing clinical-grade γδCAR-T cells has been established.
  • γδCAR-T cells represent a promising allogeneic cell therapy platform for B-cell malignancies, potentially overcoming antigen escape mechanisms.