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A Real-time Potency Assay for Chimeric Antigen Receptor T Cells Targeting Solid and Hematological Cancer Cells
Published on: November 12, 2019
EphA2 specific chimeric antigen receptor engineered T cells for the treatment of prostate cancer
Miaomiao Zhang1, Haiting Wang2, Meng Wang3
1Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China; Department of Laboratory Medicine, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China; Medical Technology School of Xuzhou Medical University, Xuzhou, Jiangsu, China.
Abstract:
Erythropoietin-producing hepatocyte receptor A2 (EphA2) is an attractive target for immunotherapy due to its high expression in a variety of solid tumors including prostate cancer. Among various types of immunotherapeutics, chimeric antigen receptor T (CAR-T) cell therapy has made promising progress in hematological and solid tumors. Here, we detected the expression of EphA2 in prostate cancer cells and developed a second-generation CAR targeting EphA2 with CD28 as a co-stimulatory receptor to explore its tumor suppressive potential for prostate cancer in vitro and in vivo. EphA2 was highly expressed on the surface of PC3 and DU145 cells. EphA2 CART cells effectively inhibited prostate cancer growth in an antigen-dependent manner in vitro and in vivo. In addition, tumor cells could stimulate the proliferation of CAR-T cells and the release of cytokine IFN-γ in vitro. These findings shed light on EphA2 as a potential target for prostate cancer, promising EphA2 specific CAR-T cells for the treatment of prostate cancer.
Insights
Chimeric antigen receptor T (CAR-T) cell therapy targeting Erythropoietin-producing hepatocyte receptor A2 (EphA2) shows promise for prostate cancer. EphA2-targeted CAR-T cells effectively suppressed tumor growth in preclinical models.
Area of Science:
- Oncology
- Immunotherapy
- Cancer Biology
Background:
- Erythropoietin-producing hepatocyte receptor A2 (EphA2) is highly expressed in various solid tumors, including prostate cancer, making it a potential target for cancer immunotherapy.
- Chimeric antigen receptor T (CAR-T) cell therapy is an emerging immunotherapeutic strategy with demonstrated efficacy in hematological malignancies and growing potential in solid tumors.
Purpose of the Study:
- To investigate the potential of targeting EphA2-expressing prostate cancer cells using a novel second-generation CAR-T cell therapy.
- To evaluate the in vitro and in vivo efficacy of EphA2-specific CAR-T cells in preclinical models of prostate cancer.
Main Methods:
- Detection of EphA2 expression on prostate cancer cell lines (PC3 and DU145).
- Development of a second-generation CAR targeting EphA2, incorporating CD28 as a co-stimulatory domain.
- Assessment of EphA2 CAR-T cell-mediated tumor suppression in vitro and in vivo models.
- Evaluation of CAR-T cell proliferation and cytokine (IFN-γ) release upon tumor cell stimulation.
Main Results:
- EphA2 was confirmed to be highly expressed on the surface of PC3 and DU145 prostate cancer cells.
- EphA2-specific CAR-T cells demonstrated significant, antigen-dependent inhibition of prostate cancer cell growth in vitro and in vivo.
- Prostate cancer cells successfully stimulated the proliferation of EphA2 CAR-T cells and induced the release of interferon-gamma (IFN-γ).
Conclusions:
- EphA2 represents a viable and promising therapeutic target for prostate cancer immunotherapy.
- EphA2-specific CAR-T cells exhibit potent anti-tumor activity and warrant further investigation for clinical application in prostate cancer treatment.
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