Chimeric antigen receptor T-cell therapy: challenges and opportunities in lung cancer

Xu, Caili; Ju, Dianwen; Zhang, Xuyao

doi:10.1093/abt/tbac006

Cited by 8 publications

(8 citation statements)

References 129 publications

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“…Abnormal nuclear structure in erythrocytes and platelets as well as excessively active DNA replication and mutation in tumor cells pose additional impediments to gene editing. As for the immune cells, genetic engineering technologies have been widely used in manufacturing immune cells with chimeric antigen receptors (CARs) (34)(35)(36)(37). Coating IR780-loaded mesoporous silica nanoparticles with GPC3-specific CAR-T cell membranes enhanced tumor-targeting capability, with tumors weighing less than half the weight of normal T cell membrane-coated nanoparticle treatment group (38).…”

Section: Immune Cellsmentioning

confidence: 99%

Cell Membrane-Derived Vesicle: A Novel Vehicle for Cancer Immunotherapy

Zhang

2022

Front. Immunol.

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As nano-sized materials prepared by isolating, disrupting and extruding cell membranes, cellular vesicles are emerging as a novel vehicle for immunotherapeutic drugs to activate antitumor immunity. Cell membrane-derived vesicles inherit the surface characteristics and functional properties of parental cells, thus having superior biocompatibility, low immunogenicity and long circulation. Moreover, the potent antitumor effect of cellular vesicles can be achieved through surface modification, genetic engineering, hybridization, drug encapsulation, and exogenous stimulation. The capacity of cellular vesicles to combine drugs of different compositions and functions in physical space provides a promising vehicle for combinational immunotherapy of cancer. In this review, the latest advances in cellular vesicles as vehicles for combinational cancer immunotherapy are systematically summarized with focuses on manufacturing processes, cell sources, therapeutic strategies and applications, providing an insight into the potential and existing challenges of using cellular vesicles for cancer immunotherapy.

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Section: Immune Cellsmentioning

confidence: 99%

Cell Membrane-Derived Vesicle: A Novel Vehicle for Cancer Immunotherapy

Zhang

2022

Front. Immunol.

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“…The lung adenocarcinoma-associated TAAs currently being investigated in clinical trials on CAR-T cells include mesothelin (MSLN), mucin 1 (MUC1), carcinoembryonic antigen (CEA) EGFR, PD-L1, prostate stem cell antigen (PSCA), disialoganglioside GD2 (GD2), and c-Met (218)(219)(220)(221)(222).…”

Section: Summary and Future Perspectivesmentioning

confidence: 99%

Drug resistance mechanisms and progress in the treatment of EGFR‑mutated lung adenocarcinoma (Review)

et al. 2022

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According to global cancer data, lung cancer was the leading cause of cancer-related death in 2020. With the diversification of treatment strategies, the survival outcomes of patients with advanced lung cancer have improved significantly, but the 5-year overall survival rate remains <20%. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are the preferred treatment for lung adenocarcinoma patients with EGFR-sensitive mutations; however, acquired drug resistance is inevitable. Osimertinib (a third-generation EGFR inhibitor) is the most commonly used drug for cancers with a secondary T790M mutation. Unfortunately, acquired drug resistance against third-generation drugs still emerges. The C797s mutation is the primary acquired resistance mechanism against Osimertinib. Research on fourth-generation EGFR-TKI drugs with a C797s mutation is currently at various experimental stages, and no drug has been approved for clinical use. In addition to the resistance mechanisms described above, HER2 amplification, MET amplification, PIK3A mutation, KRAS mutation, BRAF mutation, transformation to small cell lung cancer, transformation to lung squamous cell carcinoma, and EMT have been reported as mechanisms of acquired drug resistance to first-, second-and third-generation EGFR-TKIs. These mechanisms are noted in a relatively high proportion of tumors, but treatment options are limited. In recent years, immunotherapy has made progress in the treatment of several cancers, including advanced EGFR-mutated non-small cell lung cancer (NSCLC). Due to the relatively high frequency of EGFR mutation in patients with lung adenocarcinoma in China, an increased number of patients develop EGFR-TKI resistance, and subsequent treatment options are critical. This article reviews the mechanisms of drug resistance to different EGFR-TKIs and treatment progression, providing ideas for the follow-up treatment for EGFR-resistant patients.

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“…Nevertheless, in recent clinical trials of CAR-T cells targeting the EGFR (NCT01869166) and PD-L1 (NCT03060343) [ 18 ], such CAR-T cell therapies have shown safety and partial remission in patients. Other clinical trials that target carcinoembryonic antigen (CEA) CAR-T (NCT04348643) [ 19 ] and anti-B7-H3 CAR-T (NCT04842812) therapies [ 18 ] are also ongoing. Common challenges faced when developing CAR-T cell therapy in solid tumors, such as in lung cancer, include the heterogeneity in antigen expression, a high genomic instability within solid tumors, as well as tumor cell adaptation.…”

Section: Introductionmentioning

confidence: 99%

Cell-Surface GRP78-Targeted Chimeric Antigen Receptor T Cells Eliminate Lung Cancer Tumor Xenografts

Wang,

Wei,

Yuan

et al. 2024

IJMS

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Lung cancer is one of the most common and intractable malignancies. It is associated with low survival rates despite existing treatments, indicating that new and more effective therapies are urgently needed such as the chimeric antigen receptor-T (CAR-T) cell immunotherapy. The cell-surface glucose-regulated protein 78 (csGRP78) is expressed in various hematological malignancies and solid tumor cells including lung cancer in response to cancer-related endoplasmic reticulum stress, while GRP78 is restricted to inside the normal cells. Here, we detected the prominent expression of csGRP78 in both lung cancer cell lines, A549 and H1299, as well as cancer stemlike cells derived from A549 by immunofluorescence. Next, a csGRP78-targeted CAR was constructed, and the transduced CAR-T cells were tested for their potency to kill the two lung cancer cell lines and derived stemlike cells, which was correlated with specific interferon γ release in vitro. Finally, we found that csGRP78 CAR-T cells also efficiently killed both lung cancer cells and cancer stemlike cells, resulting into the elimination of tumor xenografts in vivo, neither with any evidence of relapse after 63 days of tumor clearance nor any detrimental impact on other body organs we examined. Our study reveals the capacity of csGRP78 as a therapeutic target and offers valuable insight into the development of csGRP78 CAR-T cells as potential therapy for lung cancer.

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Chimeric antigen receptor T-cell therapy: challenges and opportunities in lung cancer

Cited by 8 publications

References 129 publications

Cell Membrane-Derived Vesicle: A Novel Vehicle for Cancer Immunotherapy

Cell Membrane-Derived Vesicle: A Novel Vehicle for Cancer Immunotherapy

Drug resistance mechanisms and progress in the treatment of EGFR‑mutated lung adenocarcinoma (Review)

Cell-Surface GRP78-Targeted Chimeric Antigen Receptor T Cells Eliminate Lung Cancer Tumor Xenografts

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