EpCAM-targeting CAR-T cell immunotherapy is safe and efficacious for epithelial tumors

Li, Dan; Guo, Xianling; Yang, Kun; Yang, Yuening; Zhou, Weilin; Huang, Yong; Liang, Xiao; Su, Jinhua; Jiang, Lin; Li, Jing; Fu, Maorong; He, Haixia; Yang, Jinrong; Shi, Huashan; Yang, Hanshuo; Tong, Aiping; Chen, Nianyong; Hu, Jiankun; Xu, Qing; Wei, Yu-Quan; Wang, Wei

doi:10.1126/sciadv.adg9721

Cited by 17 publications

(2 citation statements)

References 57 publications

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“…Notably, these therapies are not yet approved by the FDA. EpCAM, another antigen that has been tested, is regarded as a novel target for adoptive T-cell treatment and a possible emerging biomarker for circulating tumor cells ( 110 , 111 ). EpCAM CAR-T cells show lytic cytotoxicity against target cells and secrete cytotoxic cytokines such as TNF-α and IFN-γ in an EpCAM-dependent manner.…”

Section: Gene-modified T Cell Therapymentioning

confidence: 99%

Redefining the battle against colorectal cancer: a comprehensive review of emerging immunotherapies and their clinical efficacy

Shebbo,

Binothman,

Darwaish

et al. 2024

Front. Immunol.

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Colorectal cancer (CRC) is the third most common cancer globally and presents a significant challenge owing to its high mortality rate and the limitations of traditional treatment options such as surgery, radiotherapy, and chemotherapy. While these treatments are foundational, they are often poorly effective owing to tumor resistance. Immunotherapy is a groundbreaking alternative that has recently emerged and offers new hope for success by exploiting the body’s own immune system. This article aims to provide an extensive review of clinical trials evaluating the efficacy of various immunotherapies, including CRC vaccines, chimeric antigen receptor T-cell therapies, and immune checkpoint inhibitors. We also discuss combining CRC vaccines with monoclonal antibodies, delve into preclinical studies of novel cancer vaccines, and assess the impact of these treatment methods on patient outcomes. This review seeks to provide a deeper understanding of the current state of CRC treatment by evaluating innovative treatments and their potential to redefine the prognosis of patients with CRC.

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Section: Gene-modified T Cell Therapymentioning

confidence: 99%

Redefining the battle against colorectal cancer: a comprehensive review of emerging immunotherapies and their clinical efficacy

Shebbo,

Binothman,

Darwaish

et al. 2024

Front. Immunol.

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“…Additionally, and rst clinical data shows that EpCAMdirected CAR T-cells are both safe and e cacious in the treatment of EpCAM-positive malignancies. [15] ,…”

Section: Introductionmentioning

confidence: 99%

PD-1 blockade does not improve efficacy of EpCAM-directed CAR T-cells in lung cancer brain metastasis.

Blobner,

Dengler,

Eberle

et al. 2024

Preprint

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Background Lung cancer brain metastasis have a devastating prognosis, necessitating innovative treatment strategies. While chimeric antigen receptor (CAR) T-cells show promise in hematologic malignancies, their efficacy in solid tumors, including brain metastasis, is limited by the immunosuppressive tumor environment. The PD-L1/PD-1 pathway inhibits CAR T-cell activity in the tumor microenvironment, presenting a potential target to enhance therapeutic efficacy. This study aims to evaluate the impact of anti-PD1 antibodies on CAR T-cells in treating lung cancer brain metastasis. Methods We utilized a murine immunocompetent, syngeneic orthotopic cerebral metastasis model for repetitive intracerebral two-photon laser scanning microscopy (TPLSM), enabling in vivo characterization of red fluorescent tumor cells and CAR T-cells at a single-cell level over time. Red fluorescent EpCAM-transduced Lewis Lung carcinoma cells (EpCAM/tdtLL/2 cells) were implanted intracranially. Following the formation of brain metastasis, EpCAM-directed CAR T-cells were injected into adjacent brain tissue, and animals received either anti-PD-1 or an isotype control. Results Compared to controls receiving T-cells lacking a CAR, mice receiving EpCAM-directed CAR T-cells showed higher intratumoral CAR T-cell densities in the beginning after intraparenchymal injection. This finding was accompanied with reduced tumor growth and translated into a survival benefit. Additional anti-PD1 treatment, however, did not affect intratumoral CAR T-cell persistence nor tumor growth and thereby did not provide an additional therapeutic effect. Conclusion CAR T-cell therapy for brain malignancies appears promising. However, additional anti-PD1 treatment did not enhance intratumoral CAR T-cell persistence or effector function, highlighting the need for novel strategies to improve CAR T-cell therapy in solid tumors.

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The Role of CAR-T Cells in Targeting Cancer Stem Cells

Maali,

Sharifzadeh

2024

Stem Cell Biology and Regenerative Medicine

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EpCAM-targeting CAR-T cell immunotherapy is safe and efficacious for epithelial tumors

Cited by 17 publications

References 57 publications

Redefining the battle against colorectal cancer: a comprehensive review of emerging immunotherapies and their clinical efficacy

Redefining the battle against colorectal cancer: a comprehensive review of emerging immunotherapies and their clinical efficacy

PD-1 blockade does not improve efficacy of EpCAM-directed CAR T-cells in lung cancer brain metastasis.

The Role of CAR-T Cells in Targeting Cancer Stem Cells

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