MUC1 as a target for CAR‐T therapy in head and neck squamous cell carinoma

Mei, Zi; Zhang, Kai; Lam, Alfred King‐Yin; Huang, Junhui; Qiu, Feng; Qiao, Bin; Zhang, Yi

doi:10.1002/cam4.2733

Cited by 63 publications

(56 citation statements)

References 36 publications

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“…The exogenous addition of IL-22 increases the expression of MUC1. CAR-MUC1-IL22 T cells secreting IL-22 enhance recognition and cytotoxic ability against head and neck squamous cell carcinoma [33].…”

Section: Improving Car T Cell Antigen Recognitionmentioning

confidence: 99%

Gene modification strategies for next-generation CAR T cells against solid cancers

et al. 2020

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Immunotherapies have become the backbone of cancer treatment. Among them, chimeric antigen receptor (CAR) T cells have demonstrated great success in the treatment of hematological malignancies. However, CAR T therapy against solid tumors is less effective. Antigen targeting; an immunosuppressive tumor microenvironment (TME); and the infiltration, proliferation, and persistence of CAR T cells are the predominant barriers preventing the extension of CAR T therapy to solid tumors. To circumvent these obstacles, the next-generation CAR T cells will require more potent antitumor properties, which can be achieved by gene-editing technology. In this review, we summarize innovative strategies to enhance CAR T cell function by improving target identification, persistence, trafficking, and overcoming the suppressive TME. The construction of multi-target CAR T cells improves antigen recognition and reduces immune escape. Enhancing CAR T cell proliferation and persistence can be achieved by optimizing costimulatory signals and overexpressing cytokines. CAR T cells equipped with chemokines or chemokine receptors help overcome their poor homing to tumor sites. Strategies like knocking out immune checkpoint molecules, incorporating dominant negative receptors, and chimeric switch receptors can favor the depletion or reversal of negative T cell regulators in the TME.

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Section: Improving Car T Cell Antigen Recognitionmentioning

confidence: 99%

Gene modification strategies for next-generation CAR T cells against solid cancers

et al. 2020

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“…Many investigations are still underway, to identify and validate tumor-associated antigens and how to overcome the challenges associated with CAR T cells in treating solid tumors [ 138 ]. In this regard, Mei and colleagues have recently proposed mucin-1 (MUC-1) as a target for CAR-T cells based on the higher expression of this protein by tumor cells, compared to non-neoplastic tissue and the effective cytotoxicity of MUC-1 CAR-T cells in vitro and in vivo [ 139 ].…”

Section: Discussionmentioning

confidence: 99%

Immune Checkpoints Pathways in Head and Neck Squamous Cell Carcinoma

Veigas

Mahmoud

Merlo

et al. 2021

Cancers

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Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous group of tumors usually diagnosed at an advanced stage and characterized by a poor prognosis. The main risk factors associated with its development include tobacco and alcohol consumption and Human Papillomavirus (HPV) infections. The immune system has a significant role in the oncogenesis and evolution of this cancer type. Notably, the immunosuppressive tumor microenvironment triggers immune escape through several mechanisms. The improved understanding of the antitumor immune response in solid tumors and the role of the immune checkpoint molecules and other immune regulators have led to the development of novel therapeutic strategies that revolutionized the clinical management of HNSCC. However, the limited overall response rate to immunotherapy urges identifying predictive biomarkers of response and resistance to treatment. Here, we review the role of the immune system and immune checkpoint pathways in HNSCC, the most relevant clinical findings linked to immunotherapeutic strategies and predictive biomarkers of response and future treatment perspectives.

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“…(8) Mucin1 glycoprotein 1 (MUC1) belongs to the family of human epithelial mucins [ 84 ] Its expression on normal cells is hidden from the immune system, and its aberrant glycosylation (large number of O-glycosylated tandem repeat) on tumors creates new epitopes recognized by the immune system [ 85 ]. Pre-clinical studies in vitro and in xenograft models validated MUC1 target for CAR-T therapy [ 86 , 87 ].…”

Section: Biological Rationale Of Adoptive Cell Transfer In Hepatocmentioning

confidence: 99%

Adoptive Cell Therapy in Hepatocellular Carcinoma: Biological Rationale and First Results in Early Phase Clinical Trials

Rochigneux

Chanez

Rauglaudre

et al. 2021

Cancers

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The mortality of hepatocellular carcinoma (HCC) is quickly increasing worldwide. In unresectable HCC, the cornerstone of systemic treatments is switching from tyrosine kinase inhibitors to immune checkpoints inhibitors (ICI). Next to ICI, adoptive cell transfer represents another promising field of immunotherapy. Targeting tumor associated antigens such as alpha-fetoprotein (AFP), glypican-3 (GPC3), or New York esophageal squamous cell carcinoma-1 (NY-ESO-1), T cell receptor (TCR) engineered T cells and chimeric antigen receptors (CAR) engineered T cells are emerging as potentially effective therapies, with objective responses reported in early phase trials. In this review, we address the biological rationale of TCR/CAR engineered T cells in advanced HCC, their mechanisms of action, and results from recent clinical trials.

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MUC1 as a target for CAR‐T therapy in head and neck squamous cell carinoma

Cited by 63 publications

References 36 publications

Gene modification strategies for next-generation CAR T cells against solid cancers

Gene modification strategies for next-generation CAR T cells against solid cancers

Immune Checkpoints Pathways in Head and Neck Squamous Cell Carcinoma

Adoptive Cell Therapy in Hepatocellular Carcinoma: Biological Rationale and First Results in Early Phase Clinical Trials

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