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Related Concept Videos

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.
Metastasis02:30

Metastasis

Metastasis is the spread of cancer cells from the original site to distant locations in the body. Cancer cells can spread via blood vessels (hematogenous) as well as lymph vessels in the body.
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
Mesenchymal Stem Cells01:19

Mesenchymal Stem Cells

Mesenchymal stem cells (MSCs) are adult stem cells that can differentiate into most connective tissue cell types, except for hematopoietic cells, depending upon the source of MSCs. For example, bone-marrow-derived MSCs (BM-MSCs) can differentiate into osteocytes, hepatocytes, and pancreatic and neuronal cells. MSCs can be isolated from various sources such as bone marrow, placenta, adipose tissue, teeth, and Wharton’s jelly, a gelatinous substance in the umbilical cord. The ease of their access...
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...

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Related Experiment Video

Updated: May 23, 2026

Generation and Expansion of Primary, Malignant Pleural Mesothelioma Tumor Lines
08:01

Generation and Expansion of Primary, Malignant Pleural Mesothelioma Tumor Lines

Published on: April 21, 2022

Membrane-bound TRAIL-armoring augments CAR-T cells in mesothelin-positive solid malignancies.

Alessia Volpe1, Juan Zurita1, Larissa Shenker1

  • 1Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.

Journal for Immunotherapy of Cancer
|May 21, 2026
PubMed
Summary

Engineered chimeric antigen receptor (CAR)-T cells armored with membrane-bound tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) effectively target tumors with varied antigen expression. This innovative immunotherapy enhances anti-cancer activity and improves survival in preclinical models.

Keywords:
Chimeric antigen receptor - CARImmunotherapyLung CancerMesotheliomaSolid tumor

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A Spheroid Killing Assay by CAR T Cells
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Generation and Expansion of Primary, Malignant Pleural Mesothelioma Tumor Lines
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A Spheroid Killing Assay by CAR T Cells
08:19

A Spheroid Killing Assay by CAR T Cells

Published on: December 12, 2018

Area of Science:

  • Immunotherapy
  • Oncology
  • Cellular Therapy

Background:

  • Chimeric antigen receptor (CAR)-T cell therapy targeting mesothelin (MSLN) is effective for high-MSLN tumors but limited by heterogeneous antigen expression.
  • An innovative approach involves engineering MSLN-specific (M28z) CAR-T cells to express a membrane-bound (MB)-TRAIL chimera on their surface.
  • This MB-TRAIL armor enhances CAR-T cell anticancer activity, addressing challenges posed by heterogeneous antigen expression in tumors.

Purpose of the Study:

  • To engineer and evaluate MB-TRAIL-armored MSLN-directed M28z CAR-T cells for enhanced anticancer efficacy.
  • To assess the in vitro and in vivo therapeutic potential of this novel CAR-T cell construct against tumors with heterogeneous MSLN expression.
  • To investigate the combination therapy of MB-TRAIL-armored CAR-T cells with doxorubicin for overcoming TRAIL resistance.

Main Methods:

  • Engineered MB-TRAIL-armored MSLN-directed M28z CAR-T cells and assessed in vitro toxicity against MSLN-expressing tumor cells.
  • Utilized triple-multiplex bioluminescence imaging for longitudinal, in vivo assessment of CAR-T cell dynamics and tumor responses in xenograft models (MSTO-211H PM, A549 NSCLC).
  • Evaluated the therapeutic benefit of combining MB-TRAIL-armored CAR-T cells with doxorubicin in an A549 xenograft model.

Main Results:

  • MB-TRAIL M28z CAR-T cell therapy induced apoptosis in both MSLN+ and MSLN- tumors, significantly improving survival in heterogeneous MSTO-211H PM and A549 NSCLC models.
  • The treatment provided sustained protection against metastatic spread in the MSTO-211H model.
  • Doxorubicin combination therapy overcame TRAIL resistance in the A549 model, increasing susceptibility to MB-TRAIL M28z CAR-T cells and reducing metastatic growth.

Conclusions:

  • The MB-TRAIL-armored CAR-T cell strategy demonstrates superior antitumor efficacy compared to standard M28z CAR-T cells by targeting heterogeneous antigen expression.
  • This approach provides a foundation for a new class of clinically translatable TRAIL-armored CAR-T cell immunotherapies.
  • The findings suggest potential for treating a wider range of malignancies with this enhanced CAR-T cell therapy.