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Human epidermal growth factor receptor 2 (HER2)-specific chimeric antigen receptor (CAR) for tumor immunotherapy; recent progress.

ABSTRACT: Due to the overexpression or amplification of human epidermal growth factor receptor 2 (HER2) with poor prognosis in a myriad of human tumors, recent studies have focused on HER2-targeted therapies. Deregulation in HER2 signaling pathways is accompanied by sustained tumor cells growth concomitant with their migration and also tumor angiogenesis and metastasis by stimulation of proliferation of a network of blood vessels. A large number of studies have provided clear evidence that the emerging HER2-directed treatments could be the outcome of patients suffering from HER2 positive breast and also gastric/gastroesophageal cancers. Thanks to its great anti-tumor competence, immunotherapy using HER2-specific chimeric antigen receptor (CAR) expressing immune cell has recently attracted increasing attention. Human T cells and also natural killer (NK) cells can largely be found in the tumor microenvironment, mainly contributing to the tumor immune surveillance. Such properties make them perfect candidate for genetically modification to express constructed CARs. Herein, we will describe the potential targets of the HER2 signaling in tumor cells to clarify HER2-mediated tumorigenesis and also discuss recent findings respecting the HER2-specific CAR-expressing immune cells (CAR T and CAR NK cell) for the treatment of HER2-expressing tumors.

SUBMITTER: Budi HS

PROVIDER: S-EPMC8800342 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Chimeric antigen receptor (CAR)-transduced natural killer cells in tumor immunotherapy.

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| S-EPMC5800464 | biostudies-literature

Antibody Recognition of Human Epidermal Growth Factor Receptor-2 (HER2) Juxtamembrane Domain Enhances Anti-Tumor Response of Chimeric Antigen Receptor (CAR)-T Cells.

Project description:Chimeric antigen receptor (CAR) T cell therapy shows promise in treating malignant tumors. However, the use of human epidermal growth factor receptor-2 (HER2) CAR-T cells carries the risk of severe toxicity, including cytokine release syndrome, due to their "on-target off-tumor" recognition of HER2. Enhancing the quality and functionality of HER2 CARs could greatly improve the therapeutic potential of CAR-T cells. In this study, we developed a novel anti-HER2 monoclonal antibody, Ab8, which targets domain III of HER2, distinct from the domain IV recognition of trastuzumab. Although two anti-HER2 mAbs induced similar levels of antibody-dependent cellular cytotoxicity, trastuzumab-based CAR-T cells exhibited potent antitumor activity against HER2-positive cancer cells. In conclusion, our findings provide scientific evidence that antibody recognition of the membrane-proximal domain promotes the anti-tumor response of HER2-specific CAR-T cells.

| S-EPMC11200690 | biostudies-literature

Human Epidermal Growth Factor Receptor 2 (HER2) -Specific Chimeric Antigen Receptor-Modified T Cells for the Immunotherapy of HER2-Positive Sarcoma.

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| S-EPMC4429176 | biostudies-literature

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| S-EPMC9334018 | biostudies-literature

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| S-EPMC7160013 | biostudies-literature

Chimeric Antigen Receptor T-Cells (CAR T-Cells) for Cancer Immunotherapy - Moving Target for Industry?

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| S-EPMC5982434 | biostudies-other

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Project description:We previously developed human CAR macrophages (CAR-M) and demonstrated redirection of macrophage anti-tumor function leading to tumor control in immunodeficient xenograft models. Here, we developed clinically relevant fully immunocompetent syngeneic models to evaluate the potential for CAR-M to remodel the tumor microenvironment (TME), induce T cell anti-tumor immunity, and sensitize solid tumors to PD1/PDL1 checkpoint inhibition. In vivo, anti-HER2 CAR-M significantly reduced tumor burden, prolonged survival, remodeled the TME, increased intratumoral T cell and natural killer (NK) cell infiltration, and induced epitope spreading. CAR-M therapy protected against antigen-negative relapse in a T cell dependent fashion, confirming long-term anti-tumor immunity. In HER2+ solid tumors resistant to anti-PD1(aPD1) monotherapy, the combination of CAR-M and aPD1 significantly improved tumor growth control, survival, and remodeling of the TME. These results demonstrate synergy between CAR-M and T cell checkpoint blockade and provide a strategy to enhance response to aPD1 therapy for patients with non-responsive tumors.

2024-11-20 | GSE275417 | GEO

Chimeric Antigen Receptor beyond CAR-T Cells.

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Alternative CAR Therapies: Recent Approaches in Engineering Chimeric Antigen Receptor Immune Cells to Combat Cancer.

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