Efficacy of anti-CD147 chimeric antigen receptors targeting hepatocellular carcinoma

Hsiang-Chi, Tseng; Xiong, Wei; Badeti, Saiaditya; Yang, Yan; Ma, Minh; Liu, Ting; Ramos, Carlos A.; Dotti, Gianpietro; Fritzky, Luke; Jiang, Jie; Yi, Qing; Guarrera, James V.; Zong, Wei Xing; Liu, Chen; Liu, Dongfang

doi:10.1038/s41467-020-18444-2

Cited by 118 publications

(93 citation statements)

References 81 publications

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“…In another study, T and NK cells transduced with a CD147-specific CAR could efficiently eliminate several HCC cell lines in vitro and HCC tumors in xenograft murine models. The use of logic-gated (log) GPC3-synNotch-inducible CD147-CAR for reducing on-target/off-tumor toxicity in HCC showed that LogCD147-CAR could selectively eliminate dual antigen (GPC3-positive CD147-positive), but not single antigen (GPC3-negative CD147-positive) positive HCC cells without any serious on-target/off-tumor toxicity in a human CD147 transgenic murine model ( 100 ). Besides, respecting the TGF-β capability to inhibit NK cell function, Wang and his coworkers genetically modified NK-92 cells to present a chimeric receptor with TGF-β type II receptor extracellular and transmembrane domains associated with intracellular domain of NKG2D, termed as TN chimeric receptor.…”

Section: Car Nk Cells In Solid Tumorsmentioning

confidence: 99%

RETRACTED: CAR-NK Cell: A New Paradigm in Tumor Immunotherapy

et al. 2021

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The tumor microenvironment (TME) is greatly multifaceted and immune escape is an imperative attribute of tumors fostering tumor progression and metastasis. Based on reports, the restricted achievement attained by T cell immunotherapy reflects the prominence of emerging other innovative immunotherapeutics, in particular, natural killer (NK) cells-based treatments. Human NK cells act as the foremost innate immune effector cells against tumors and are vastly heterogeneous in the TME. Currently, there exists a rapidly evolving interest in the progress of chimeric antigen receptor (CAR)-engineered NK cells for tumor immunotherapy. CAR-NK cells superiorities over CAR-T cells in terms of better safety (e.g., absence or minimal cytokine release syndrome (CRS) and graft-versus-host disease (GVHD), engaging various mechanisms for stimulating cytotoxic function, and high feasibility for ‘off-the-shelf’ manufacturing. These effector cells could be modified to target various antigens, improve proliferation and persistence in vivo, upturn infiltration into tumors, and defeat resistant TME, which in turn, result in a desired anti-tumor response. More importantly, CAR-NK cells represent antigen receptors against tumor-associated antigens (TAAs), thereby redirecting the effector NK cells and supporting tumor-related immunosurveillance. In the current review, we focus on recent progress in the therapeutic competence of CAR-NK cells in solid tumors and offer a concise summary of the present hurdles affecting therapeutic outcomes of CAR-NK cell-based tumor immunotherapies.

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Section: Car Nk Cells In Solid Tumorsmentioning

confidence: 99%

RETRACTED: CAR-NK Cell: A New Paradigm in Tumor Immunotherapy

et al. 2021

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“…An open label early phase I clinical trial has started to recruit patients with recurrent GBM to test the safety, tolerance and efficacy of treatment with CD147-specific CAR T cells (NCT04045847). While CD147 is overexpressed on malignant cells, it is still expressed at a low level on various normal tissues such as epithelial and endothelial cells, and brain and heart tissue ( Riethdorf et al, 2006 ; Liao et al, 2011 ; Tseng et al, 2020 ). Therefore, there is a concern that CD147-specific CAR T cells may cause on-target off-tumor side effects.…”

Section: Targets Of Car T Cell Therapy In On-going Clinical Trialsmentioning

confidence: 99%

CAR T Cell-Based Immunotherapy for the Treatment of Glioblastoma

et al. 2021

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Glioblastoma multiforme (GBM) is the most common and aggressive malignant primary brain tumor in adults. Current treatment options typically consist of surgery followed by chemotherapy or more frequently radiotherapy, however, median patient survival remains at just over 1 year. Therefore, the need for novel curative therapies for GBM is vital. Characterization of GBM cells has contributed to identify several molecules as targets for immunotherapy-based treatments such as EGFR/EGFRvIII, IL13Rα2, B7-H3, and CSPG4. Cytotoxic T lymphocytes collected from a patient can be genetically modified to express a chimeric antigen receptor (CAR) specific for an identified tumor antigen (TA). These CAR T cells can then be re-administered to the patient to identify and eliminate cancer cells. The impressive clinical responses to TA-specific CAR T cell-based therapies in patients with hematological malignancies have generated a lot of interest in the application of this strategy with solid tumors including GBM. Several clinical trials are evaluating TA-specific CAR T cells to treat GBM. Unfortunately, the efficacy of CAR T cells against solid tumors has been limited due to several factors. These include the immunosuppressive tumor microenvironment, inadequate trafficking and infiltration of CAR T cells and their lack of persistence and activity. In particular, GBM has specific limitations to overcome including acquired resistance to therapy, limited diffusion across the blood brain barrier and risks of central nervous system toxicity. Here we review current CAR T cell-based approaches for the treatment of GBM and summarize the mechanisms being explored in pre-clinical, as well as clinical studies to improve their anti-tumor activity.

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“…Another marker of interest is CD147 (also known as basigin), which is present at low levels in different cell types, including hematopoietic, epithelial, and endothelial, and is found highly expressed in a variety of cancer cells. Recently, it was shown that CAR-T cells recognizing CD147 could effectively kill HCC cell lines in vitro and inhibit xenograft growth in mouse models 286 and are now being tested in a phase 1 clinical trial (NCT03993743). Meanwhile, EpCAM-recognizing CAR-T cells are being tested in clinical trials for the treatment of epithelial cancers, with two of them having a particular focus on HCC (NCT02729493 and NCT03013712), while one ongoing phase 1/2 clinical trial is aiming to test the efficacy of anti-MET cells in HCC and other malignancies (NCT03638206).…”

Section: Adoptive Cell Therapy (Act)mentioning

confidence: 99%

The therapeutic landscape of hepatocellular carcinoma

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García‐Beccaria

Szydlowska

et al. 2021

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The liver is endowed with an amazing regenerative capacity that allows it to withstand an enormous amount of damage. Nevertheless, it is precisely this highly regenerative capacity that renders it susceptible to dysplasia and liver cancer. Liver cancer is not only one of the most common cancers but also one of the deadliest. Hepatocellular carcinoma (HCC) is the most common form of liver cancer, accounting for up to 70%-90% of all cases, but treatment options for advanced stages remain scarce. Therefore, a great deal of effort has gone into identifying early diagnostic markers as well as novel therapies, both local and systemic, for the treatment of this deadly disease. In this review, we aim to shed light into the current therapeutic landscape of HCC with an emphasis on the available treatments, ranging from surgical and local-ablative therapy for early and intermediate stages of the disease to systemic therapies for advanced cancer treatments. We will also address the molecular mechanisms and limitations of currently available systemic therapies and the causes of treatment resistance and finally summarize the emerging future avenues and novel concepts that are promising.

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Efficacy of anti-CD147 chimeric antigen receptors targeting hepatocellular carcinoma

Cited by 118 publications

References 81 publications

RETRACTED: CAR-NK Cell: A New Paradigm in Tumor Immunotherapy

RETRACTED: CAR-NK Cell: A New Paradigm in Tumor Immunotherapy

CAR T Cell-Based Immunotherapy for the Treatment of Glioblastoma

The therapeutic landscape of hepatocellular carcinoma

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