Immunotherapy of Non-Small Cell Lung Cancer

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Immunology and Immunotherapy".

Deadline for manuscript submissions: 20 September 2025 | Viewed by 4450

Special Issue Editor


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Guest Editor
Division of Hematology and Oncology, Department of Medicine, The University of Alabama at Birmingham, Birmingham, AL, USA
Interests: oncology and carcinogenesis; thoracic oncology; tumour immunology

Special Issue Information

Dear Colleagues,

Antibody Drug Conjugates (ADCs) are the newer classes of immunotherapy drugs which present a promising but challenging therapeutic approach for Non-small cell lung cancer (NSCLC). They have shown promise in treating patients who have developed resistance to other therapies. Several ADCs are in clinical trial, targeting various antigens including TROP2, HER2 etc. Despite the promise, ADCs face significant challenges in NSCLC treatment including toxicity like interstitial lung disease (ILD), limited efficacy, identifying suitable surface targets and resistance. There is insufficient knowledge about how ADC targets are expressed in the body. A more thorough analysis of this expression could lead to a better understanding of adverse events, such as ILD. This improved understanding may help reduce the occurrence of these adverse effects. Our study aims to analyze the ADC target expression in lung tissue to help us understand the relation between ADCs and interstitial lung disease.

We look forward to receiving your contributions.

Dr. Aakash P. Desai
Guest Editor

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Keywords

  • antibody drug conjugates
  • ADCs
  • non-small cell lung cancer
  • NSCLC
  • interstitial lung disease
  • ILD
  • TROP2
  • ERBB2

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Published Papers (2 papers)

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Research

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8 pages, 1697 KiB  
Article
Association of Antibody–Drug Conjugate (ADC) Target Expression and Interstitial Lung Disease (ILD) in Non-Small-Cell Lung Cancer (NSCLC): Association or Causation or Neither?
by Aakash Desai, Vivek Subbiah, Sinchita Roy-Chowdhuri, Ajay Sheshadri, Sameer Deshmukh and Solange Peters
Cancers 2024, 16(22), 3753; https://doi.org/10.3390/cancers16223753 - 7 Nov 2024
Cited by 1 | Viewed by 3470
Abstract
Introduction: Non-small-cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality worldwide, despite advances in immune checkpoint inhibitors and targeted therapies. Antibody–drug conjugates (ADCs) represent a promising therapeutic approach by delivering cytotoxic agents specifically to cancer cells, potentially reducing harm to healthy [...] Read more.
Introduction: Non-small-cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality worldwide, despite advances in immune checkpoint inhibitors and targeted therapies. Antibody–drug conjugates (ADCs) represent a promising therapeutic approach by delivering cytotoxic agents specifically to cancer cells, potentially reducing harm to healthy tissues. This study aims to explore the effectiveness and challenges associated with ADCs in NSCLC, with a focus on drug-induced interstitial lung disease (D-ILD). Methods: A comprehensive literature review was conducted across MEDLINE (Ovid), Embase (Elsevier), CENTRAL (Cochrane Library), and other sources up to March 2023, to identify ADCs used in NSCLC treatment and their associated risk of D-ILD. The incidence of ILD was analyzed from clinical trial data, while ADC target expression was examined through RNA and protein levels in normal and tumor lung tissues. Discussion: Our findings highlight the therapeutic potential of ADCs in NSCLC, as evidenced by significant clinical outcomes. However, the occurrence of D-ILD presents a notable challenge, as its incidence was not directly correlated with the expression levels of the target antigens. This suggests that D-ILD may result from factors beyond antigen expression, including the cytotoxic payload and linker characteristics of ADCs. Conclusion: ADCs offer a promising avenue for NSCLC treatment. Nonetheless, the risk of D-ILD necessitates a balanced approach in ADC development, focusing on optimizing linker and payload properties to mitigate this adverse effect. Further research is essential to better understand and manage D-ILD, ensuring the safe and effective use of ADCs in clinical practice. Full article
(This article belongs to the Special Issue Immunotherapy of Non-Small Cell Lung Cancer)
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Review

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30 pages, 4062 KiB  
Review
Tumour- and Non-Tumour-Associated Factors That Modulate Response to PD-1/PD-L1 Inhibitors in Non-Small Cell Lung Cancer
by Maryam Khalil and Ming-Sound Tsao
Cancers 2025, 17(13), 2199; https://doi.org/10.3390/cancers17132199 - 30 Jun 2025
Cited by 1 | Viewed by 726
Abstract
The interaction of programmed cell death receptor 1 (PD-1) on the surface of immune cells with its ligand, programmed cell death ligand 1 (PD-L1), expressed on tumour cells and antigen-presenting cells, leads to tumour immune evasion. Antibodies that target either PD-1 or its [...] Read more.
The interaction of programmed cell death receptor 1 (PD-1) on the surface of immune cells with its ligand, programmed cell death ligand 1 (PD-L1), expressed on tumour cells and antigen-presenting cells, leads to tumour immune evasion. Antibodies that target either PD-1 or its ligand PD-L1 have shown a favourable response in cancer patients, especially those with non-small cell lung cancer (NSCLC). However, only 15 to 25% of advanced NSCLC patients will benefit from immunotherapy. The PD-L1 tumour proportion score (TPS) is the current standard biomarker to select patients for PD-1/PD-L1 blockade therapy, as patients with a high PD-L1 TPS show better response compared to patients with a low PD-L1 TPS. However, since PD-L1 expression is a continuous variable and is an imperfect biomarker, investigation into additional predictive markers is warranted. This review focuses on tumour- and non-tumour-associated factors that have been shown to affect the response to PD-1/PD-L1 inhibitors in NSCLC. We also delve into mechanistic and clinical evidence on these potential biomarkers and their relationship to the tumour microenvironment (TME). Full article
(This article belongs to the Special Issue Immunotherapy of Non-Small Cell Lung Cancer)
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