Next-Gen Systemic Therapies in NSCLC: ADCs, Vaccines, and Cell-Based Treatments

Advancements in the treatment of non-small cell lung cancer (NSCLC) have dramatically changed patient outcomes over the past decade, especially with the introduction of immune checkpoint inhibitors and targeted therapies. Despite these significant progresses, many patients experience resistance or relapse, highlighting a critical need for further innovation in systemic therapies. Current research is now intensely focused on novel therapeutic modalities that transcend traditional approaches, including the development and clinical testing of antibody-drug conjugates (ADCs), therapeutic vaccines, and a spectrum of engineered cell-based treatments. Recent studies suggest these next-generation agents may offer improved tumor targeting, overcome established resistance mechanisms, and achieve durable remissions even in patient populations refractory to existing standards of care. However, questions remain regarding patient selection, optimal sequencing, mechanism-driven combination strategies, and long-term safety.This Research Topic aims to advance the understanding and clinical relevance of next-generation systemic therapies in NSCLC, with a sharp focus on ADCs, vaccines, and cell-based immunotherapies. The goal is to gather cutting-edge research and expert perspectives that elucidate novel mechanisms of action, define biomarkers for therapy selection, and report on efficacy, resistance, toxicity, and real-world application. Specifically, this collection seeks to address outstanding scientific and clinical questions such as: what underpins differential responses to these novel modalities; how can resistance and toxicity be mitigated; and what strategies will most effectively move these therapies toward broader clinical adoption?The scope of this Research Topic encompasses systemic therapies for NSCLC—excluding studies confined to immune checkpoint inhibition or kinase inhibitors. We are particularly interested in experimental, clinical, and translational studies that investigate the therapeutic innovation, patient stratification, and practical implementation of ADCs, cancer vaccines, and cell-based treatments. To gather further insights into next-generation systemic strategies in NSCLC, we welcome articles addressing, but not limited to, the following themes:- Mechanistic studies of antibody-drug conjugates (ADCs), including target selection and resistance biology- Development and clinical evaluation of neoantigen-based, mRNA, and vector-based cancer vaccines- Novel cell-based therapies such as CAR-T, TCR-T, NK cell, and TIL approaches in solid tumors- Bispecific antibodies and T-cell engagers in the context of systemic NSCLC treatment- Sequencing and combination strategies with emerging systemic agents- Biomarker development for patient selection and therapeutic monitoring in next-gen therapies- Management of immune-related and off-target adverse events, including real-world safety data.Submissions must demonstrate clear clinical or translational relevance. Manuscripts based solely on computational modeling or predictions from public datasets without laboratory or clinical validation will not be considered.Dr Quincy Chu declares that they have received advisory board fees and/or honoraria from AbbVie, Amgen, AnHeart, Astellas, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, Geneprix, GSK, Janssen, Jazz, Merck, Novartis, Ocellaris, Pfizer, Regeneron, Sanofi, Roche, and Takeda. They have also received research grants and/or support for clinical trials from Amgen, AstraZeneca, Arrivent, Avistone, BeiGene, BlossomHill Therapeutics, Boehringer Ingelheim, Bristol Myers Squibb/TP Therapeutics, Conjupro, Daiichi Sankyo, Eikon, Eli Lilly/Loxo Oncology, Esperas, Genmab, GSK, iTEOS Therapeutics, Medlink, Merck, Merus, MonteRosa Therapeutics, Nuvalent, Pfizer, Roche, and SignalChem Biopharma.Dr. Paul Wheatley-Price declares that they have attended advisory boards for Merck, Astra Zeneca, Boehringer Ingelheim, Johnson & Johnson, Regeneron, Pfizer, BMS, GSK, Daiichi Sankyo, Novartis and Amgen. They have received speaker fees from BMS, Regeneron, Novartis, Roche, Boehringer Ingelheim and Merck. They have received research funding from Pfizer. They also declare they run clinical trials with BMS, GSK, Astra Zeneca and Summit Therapeutics. Topic editors: Quincy Siu-chung Chu, Paul Wheatley-Price Source: https://www.frontiersin.org/research-topics/79569/next-gen-systemic-therapies-in-nsclc-adcs-vaccines-and-cell-based-treatments