Related Experiment Video

Updated: Jul 10, 2026

A Syngeneic Mouse B-Cell Lymphoma Model for Pre-Clinical Evaluation of CD19 CAR T Cells
12:16

A Syngeneic Mouse B-Cell Lymphoma Model for Pre-Clinical Evaluation of CD19 CAR T Cells

Published on: October 16, 2018

Genetic Mutation and Epigenetic Silencing Drive Antigen-Negative Relapse in CD7 CAR-T Treated T-cell Lymphoid

Rongrong Chen1, Haiqiong Zheng2, Wenxin Wang2

  • 1the first Affiliated Hospital, School of Medicine, Zhejiang University Hangzhou China.

Blood Cancer Discovery
|July 8, 2026
PubMed

Insights

CD7 CAR-T therapy faces relapse challenges due to antigen loss. This study reveals genetic mutations and promoter hypermethylation as key mechanisms driving CD7 loss in T-cell malignancies.

Area of Science:

  • Oncology
  • Immunotherapy
  • Genetics

Background:

  • CD7 is a target for CAR T-cell therapy in T-cell malignancies.
  • Antigen loss leading to relapse is a significant challenge in CAR T-cell therapy.

Purpose of the Study:

  • To investigate the mechanisms of CD7 loss in patients with T-cell lymphoid malignancies relapsing after CD7 CAR-T cell therapy.

Main Methods:

  • Systematic analysis of paired pre-treatment and relapsed specimens from 10 patients.
  • Genetic sequencing and epigenetic analysis (promoter methylation) were performed.

Main Results:

  • Three mechanisms of CD7 loss were identified: frameshift mutations (2/10 patients), CD7 promoter hypermethylation (7/10 patients), and combined mutations/hypermethylation (1/10 patients).
  • Clonal heterogeneity and epigenetic plasticity were observed as drivers of relapse.

Conclusions:

  • CD7 loss, driven by genetic mutations and/or epigenetic alterations, is a critical mechanism of relapse in CD7 CAR-T cell therapy for T-cell malignancies.
  • Understanding these mechanisms is crucial for developing strategies to overcome antigen-negative relapse.

More Related Videos

Draining Lymph Node Metastasis Model for Assessing the Dynamics of Antigen-Specific CD8+ T Cells During Tumorigenesis07:45

Draining Lymph Node Metastasis Model for Assessing the Dynamics of Antigen-Specific CD8+ T Cells During Tumorigenesis

Published on: January 26, 2024

A Nonviral Approach to Generate Transient Chimeric Antigen Receptor T Cells Using mRNA for Cancer Immunotherapy09:56

A Nonviral Approach to Generate Transient Chimeric Antigen Receptor T Cells Using mRNA for Cancer Immunotherapy

Published on: February 21, 2025

Related Concept Videos

T Cell Activation and Clonal Selection01:22

T Cell Activation and Clonal Selection

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...
Tumor Immunotherapy01:27

Tumor Immunotherapy

Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
Cytotoxic T Cells-mediated Immune Response01:27

Cytotoxic T Cells-mediated Immune Response

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...
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...