Endobronchial Intratumoral Immuno- and Gene Therapies in Lung Cancer: Mechanisms of Local Delivery, Systemic Immune Effects, and Global Feasibility
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Published on: February 12, 2017
Mihai Olteanu1, Gabriela Marina Andrei1, Ramona Cioboată1
1Department of Internal Medicine-Pneumology, Faculty of Medicine, University of Medicine and Pharmacy from Craiova, 200349 Craiova, Romania.
Abstract:
Lung cancer remains the leading cause of cancer-related mortality worldwide, and durable benefit from immune checkpoint inhibitors is limited by immune exclusion, microenvironmental immunosuppression, and toxicity. This narrative translational review evaluates whether endobronchial intratumoral delivery of immuno- and gene-based therapies can transform bronchoscopic access into a therapeutic platform linking local tumour intervention with systemic antitumour immunity. We synthesise evidence on endobronchial ultrasound, electromagnetic navigation bronchoscopy, and robotic-assisted bronchoscopy, together with local checkpoint blockade, cytokine and mRNA-lipid nanoparticle constructs, oncolytic virotherapy, dendritic-cell approaches, viral and non-viral gene transfer, and enzyme- or metabolite-based strategies. Current clinical evidence remains preliminary, consisting mainly of Phase I trials, small prospective cohorts, and case-based signals, with feasibility and safety observations but no completed randomised trial demonstrating efficacy against standard-of-care systemic therapy. The most plausible candidates are patients with advanced or recurrent NSCLC, bronchoscopically accessible lesions, inadequate response to systemic immunotherapy, and immune-excluded or locally immunosuppressed tumours. Biomarkers such as PD-L1, tumour mutational burden, CD8+ infiltration, tertiary lymphoid structures, radiomics, and circulating tumour DNA require validation. This review integrates delivery technology, immune mechanisms, statistical evidence appraisal, biomarker limitations, AI-guided planning, and global feasibility.
Insights
Endobronchial delivery of immunotherapy and gene therapy shows promise for lung cancer, potentially overcoming treatment resistance. Further research is needed to confirm efficacy and guide patient selection for this localized approach.
Area of Science:
- Pulmonology and Oncology
- Immunotherapy Research
- Translational Medicine
Background:
- Lung cancer is a leading cause of cancer mortality globally.
- Immune checkpoint inhibitors (ICIs) offer durable benefit but face limitations like immune exclusion and toxicity.
- Novel therapeutic platforms are needed to enhance local tumor intervention and systemic anti-tumor immunity.
Purpose of the Study:
- To evaluate endobronchial intratumoral delivery of immuno- and gene-based therapies as a novel bronchoscopic therapeutic platform.
- To explore the potential of linking local tumor intervention with systemic anti-tumor immunity.
- To synthesize current evidence on advanced bronchoscopy techniques and various local immunotherapies.
Main Methods:
- Narrative translational review synthesizing evidence on advanced bronchoscopy (EBUS, ENB, robotic-assisted).
- Review of local therapies including checkpoint blockade, cytokine/mRNA constructs, oncolytic virotherapy, dendritic cells, and gene transfer.
- Appraisal of preliminary clinical evidence (Phase I trials, cohorts) and biomarker data.
Main Results:
- Current clinical evidence is preliminary, primarily from Phase I trials and small cohorts, focusing on feasibility and safety.
- No randomized trials have demonstrated efficacy against standard-of-care systemic therapy.
- Potential candidates include advanced/recurrent NSCLC with accessible lesions, poor ICI response, and immune-excluded/suppressed tumors.
Conclusions:
- Endobronchial delivery of novel immunotherapies presents a potential strategy to enhance anti-tumor immunity in lung cancer.
- Further rigorous clinical trials are necessary to establish efficacy and optimize patient selection.
- Validation of biomarkers and integration with AI-guided planning are crucial for future development.
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