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Updated: May 17, 2025

Advances in Human Induced Pluripotent Stem Cell-Derived Chimeric Antigen Receptor-Expressing Natural Killer Cells
Published on: February 14, 2025
Developing CAR-T/NK cells that target EphA2 for non-small cell lung cancer treatment
Seok Min Kim1, Soo Yun Lee1, Seo In Kim2,3
1Center for Gene & Cell Therapy, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea.
Introduction:
Chimeric antigen receptor (CAR) immunotherapy has revolutionized anticancer therapy, as it accurately targets cancer cells by recognizing specific antigens expressed in cancer cells. This innovative therapeutic strategy has attracted considerable attention. However, few therapeutics are available for treating non-small cell lung cancer (NSCLC), which accounts for most lung cancer cases and is one of the deadliest cancers with low survival rates.
Methods:
In this study, we developed a new antibody targeting erythropoietin-producing hepatocellular carcinoma A2 (EphA2), which is highly expressed in NSCLC, and established CAR-T/ natural killer (NK) immune cells to verify its potential for immune cell therapy. The killing capacity, cytokine secretion and solid tumor growth inhibition of EphA2 CAR-T/NK cells were compared to normal T/NK cells.
Results:
EphA2 CAR-T cells demonstrated superior killing capacity, enhanced cytokine secretion, and significant solid tumor growth inhibition. Additionally, they exhibited improved tumor infiltration in lung cancer models compared to normal T cells. The anticancer efficacy of the developed EphA2 CAR-NK cells was also confirmed, showcasing their potential as robust candidates for immune cell therapy.
Discussion:
The findings of this study highlight the potential of CAR-T/NK cell therapy targeting EphA2 as an effective treatment for lung cancer, particularly NSCLC with high EphA2 expression. By leveraging the specific targeting capabilities of CAR-T cells and the unique properties of CAR-NK cells, this approach provides a promising therapeutic strategy to address the unmet needs in NSCLC treatment.
Insights
Chimeric antigen receptor (CAR) T/NK cell therapy targeting erythropoietin-producing hepatocellular carcinoma A2 (EphA2) shows promise for non-small cell lung cancer (NSCLC). This novel approach enhances immune cell efficacy against EphA2-expressing lung tumors.
Area of Science:
- Immunotherapy
- Oncology
- Cellular Therapy
Background:
- Chimeric antigen receptor (CAR) immunotherapy offers targeted anticancer treatment.
- Non-small cell lung cancer (NSCLC) remains a deadly cancer with limited therapeutic options.
- Erythropoietin-producing hepatocellular carcinoma A2 (EphA2) is highly expressed in NSCLC.
Purpose of the Study:
- To develop and evaluate novel CAR-T and CAR-NK immune cells targeting EphA2 for NSCLC treatment.
- To assess the therapeutic potential of EphA2-targeted CAR immune cells in preclinical lung cancer models.
Main Methods:
- Development of a new antibody targeting EphA2.
- Establishment of EphA2-specific CAR-T and CAR-NK immune cells.
- Comparison of EphA2 CAR-T/NK cells with normal T/NK cells regarding killing capacity, cytokine secretion, and tumor growth inhibition in lung cancer models.
Main Results:
- EphA2 CAR-T cells exhibited superior killing, enhanced cytokine secretion, and significant solid tumor growth inhibition.
- CAR-T cells showed improved tumor infiltration in lung cancer models.
- EphA2 CAR-NK cells demonstrated confirmed anticancer efficacy.
Conclusions:
- CAR-T/NK cell therapy targeting EphA2 presents a promising strategy for NSCLC treatment.
- This approach addresses unmet needs in lung cancer therapy, particularly for tumors with high EphA2 expression.

