Lung cancer and oncolytic virotherapy——enemy's enemy

Li, Zhang; Zhang, Feiyue; Li, Gaofeng; Liang, Haifeng

doi:10.1016/j.tranon.2022.101563

Cited by 10 publications

(3 citation statements)

References 62 publications

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“…There are currently 14 clinical trials of lung cancer-associated oncolytic viruses. [ 53 ] Oncolytic viruses are designed to preferentially infect and replicate in tumors, which not only promotes cell death but also enhances immune mediators entering the tumor microenvironment and induces systemic anti-tumor immunity. Phase 1 study of intravenous administration of the chimeric adenovirus enadenotucirev in patients undergoing primary tumor resection (previously known as ColoAd1), a tumor-selective chimeric adenovirus, stimulated local high anti-tumor immune response and the infiltration of CD8 + T cells in NSCLC.…”

Section: Immunotherapy For Lung Cancermentioning

confidence: 99%

Recent advances and remaining challenges in lung cancer therapy

Barr,

Ma,

et al. 2024

Chinese Medical Journal

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Lung cancer remains the most common cause of cancer death. Given the continued research into new drugs and combination therapies, outcomes in lung cancer have been improved, and clinical benefits have been expanded to a broader patient population. However, the overall cure and survival rates for lung cancer patients remain low, especially in metastatic cases. Among the available lung cancer treatment options, such as surgery, radiation therapy, chemotherapy, targeted therapies, and alternative therapies, immunotherapy has shown to be the most promising. The exponential progress in immuno-oncology research and recent advancements made in the field of immunotherapy will further increase the survival and quality of life for lung cancer patients. Substantial progress has been made in targeted therapies using tyrosine kinase inhibitors and monoclonal antibody immune checkpoint inhibitors with many FDA-approved drugs targeting the programmed cell death ligand-1 (PD-L1) protein (e.g., durvalumab, atezolizumab), the programmed cell death-1 (PD-1) receptor (e.g., nivolumab, pembrolizumab), and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) (e.g., tremelimumab, ipilimumab). Cytokines, cancer vaccines, adoptive T cell therapies, and NK cell mono- and combinational therapies are rapidly being studied, yet to date, there are currently none that are FDA-approved for the treatment of lung cancer. In this review, we discuss the current lung cancer therapies with an emphasis on immunotherapy, including the challenges for future research and clinical applications.

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Section: Immunotherapy For Lung Cancermentioning

confidence: 99%

Recent advances and remaining challenges in lung cancer therapy

Barr,

Ma,

et al. 2024

Chinese Medical Journal

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“…Lung cancer is a serious life-threatening disease, and non-small cell lung cancer (NSCLC) is one of its most prevalent subtypes ( 1 , 2 ). Immune checkpoint inhibitors (ICIs), as PD-1/PD-L1 inhibitors based immunotherapy has made revolutionized effects and become a milestone in the treatment history of NSCLC ( 3 ). However, PD-1/PD-L1 blockade can lead to an unsatisfactory response pattern characterized by accelerated tumor growth and associated with poor prognosis——Hyperprogressive Disease (HPD) ( 4 ).…”

Section: Introductionmentioning

confidence: 99%

Hyperprogressive disease in non-small cell lung cancer after PD-1/PD-L1 inhibitors immunotherapy: underlying killer

Li¹,

Chen²,

Nie³

et al. 2023

Front. Immunol.

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Immune checkpoint inhibitors (ICIs) target the negative regulatory pathway of T cells and effectively reactive the anti-tumor immune function of T cells by blocking the key pathway of the immune escape mechanism of the tumor—PD-1/PD-L1, and fundamentally changing the prospect of immunotherapy for non-small cell lung cancer patients. However, such promising immunotherapy is overshadowed by Hyperprogressive Disease, a response pattern associated with unwanted accelerated tumor growth and characterized by poor prognosis in a fraction of treated patients. This review comprehensively provides an overview of Hyperprogressive Disease in immune checkpoint inhibitor-based immunotherapy for non-small cell lung cancer including its definition, biomarkers, mechanisms, and treatment. A better understanding of the black side of immune checkpoint inhibitors therapy will provide a more profound insight into the pros and cons of immunotherapy.

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“…Oncolytic virotherapy is a promising approach because of its potential to overcome ICIs resistance and improve outcomes in the treatment of advanced NSCLC. 8 …”

Section: Introductionmentioning

confidence: 99%

Effective intravenous delivery of adenovirus armed with TNFα and IL-2 improves anti-PD-1 checkpoint blockade in non-small cell lung cancer

et al. 2023

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Lung cancer remains among the most difficult-to-treat malignancies and is the leading cause of cancer-related deaths worldwide. The introduction of targeted therapies and checkpoint inhibitors has improved treatment outcomes; however, most patients with advanced-stage non-small cell lung cancer (NSCLC) eventually fail these therapies. Therefore, there is a major unmet clinical need for checkpoint refractory/resistant NSCLC. Here, we tested the combination of aPD-1 and adenovirus armed with TNFα and IL-2 (Ad5-CMV-mTNFα/mIL-2) in an immunocompetent murine NSCLC model. Moreover, although local delivery has been standard for virotherapy, treatment was administered intravenously to facilitate clinical translation and putative routine use. We showed that treatment of tumor-bearing animals with aPD-1 in combination with intravenously injected armed adenovirus significantly decreased cancer growth, even in the presence of neutralizing antibodies. We observed an increased frequency of cytotoxic tumor-infiltrating lymphocytes, including tumor-specific cells. Combination treatment led to a decreased percentage of immunosuppressive tumor-associated macrophages and an improvement in dendritic cell maturation. Moreover, we observed expansion of the tumor-specific memory T cell compartment in secondary lymphoid organs in the group that received aPD-1 with the virus. However, although the non-replicative Ad5-CMV-mTNFα/mIL-2 virus allows high transgene expression in the murine model, it does not fully reflect the clinical outcome in humans. Thus, we complemented our findings using NSCLC ex vivo models fully permissive for the TNFα and IL-2- armed oncolytic adenovirus TILT-123. Overall, our data demonstrate the ability of systemically administered adenovirus armed with TNFα and IL-2 to potentiate the anti-tumor efficacy of aPD-1 and warrant further investigation in clinical trials.

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Lung cancer and oncolytic virotherapy——enemy's enemy

Cited by 10 publications

References 62 publications

Recent advances and remaining challenges in lung cancer therapy

Recent advances and remaining challenges in lung cancer therapy

Hyperprogressive disease in non-small cell lung cancer after PD-1/PD-L1 inhibitors immunotherapy: underlying killer

Effective intravenous delivery of adenovirus armed with TNFα and IL-2 improves anti-PD-1 checkpoint blockade in non-small cell lung cancer

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