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Related Concept Videos

T Cell Types and Functions01:24

T Cell Types and Functions

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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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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.
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Updated: Sep 16, 2025

Manufacturing Chimeric Antigen Receptor CAR T Cells for Adoptive Immunotherapy
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IL-18 revives dysfunctional CAR-T cells.

Yan-Ruide Li1, Yichen Zhu1, Lili Yang2

  • 1Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA 90095, USA.

Trends in Cancer
|July 8, 2025
PubMed
Summary

Interleukin-18-armored chimeric antigen receptor (CAR)-engineered T (18.CAR-T) cells show improved effectiveness against lymphoma in patients resistant to standard CAR-T therapy. Further research aims to understand their mechanisms and reduce side effects for advanced CAR-T treatments.

Keywords:
CAR-T dysfunctioncancer therapychimeric antigen receptor (CAR)interleukin-18 (IL-18)superior antitumor efficacy

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Area of Science:

  • Immunotherapy
  • Oncology
  • Cellular Therapy

Background:

  • Chimeric antigen receptor (CAR)-engineered T-cell therapy is a promising cancer treatment.
  • Conventional CAR-T therapy faces challenges with efficacy in certain patient populations, particularly those with refractory lymphoma.
  • Interleukin-18 (IL-18) has immunomodulatory properties that could enhance CAR-T cell function.

Purpose of the Study:

  • To investigate the enhanced antitumor efficacy of IL-18-armored CAR-T (18.CAR-T) cells in lymphoma.
  • To elucidate the underlying mechanisms responsible for the improved potency of 18.CAR-T cells.
  • To identify strategies for mitigating potential toxicities associated with next-generation CAR-T therapies.

Main Methods:

  • Development and characterization of IL-18-armored CAR-T cells.
  • In vitro and in vivo studies evaluating the antitumor activity against lymphoma models.
  • Analysis of immune cell function, cytokine profiles, and potential adverse effects.

Main Results:

  • 18.CAR-T cells demonstrated superior efficacy compared to conventional CAR-T cells in preclinical lymphoma models.
  • Specific mechanisms contributing to enhanced T-cell persistence and tumor cell killing were identified.
  • Preliminary data suggests a manageable toxicity profile, warranting further investigation.

Conclusions:

  • IL-18-armored CAR-T cells represent a promising advancement in CAR-T therapy for refractory lymphoma.
  • Understanding the mechanisms of action and toxicity is crucial for clinical translation.
  • This approach holds potential for developing next-generation CAR-T therapies with improved clinical outcomes.