Precision immuno-oncology in NSCLC: integrating ADCs, therapeutic vaccines, and adoptive cell therapies for next-generation systemic treatment

Abstract

Targeted therapy and immune checkpoint inhibition have improved the treatment of non-small cell lung cancer (NSCLC); however, it remains one of the leading causes of cancer-related mortality worldwide. While all these therapeutic strategies have yielded clinical benefit in specific patient groups, resistance and tumor heterogeneity, short-term responses, and immune evasion remain current challenges in long-term therapeutic success. These constraints have led to the exploration of new precision immuno-oncology approaches for more specific targeting more efficient stimulation of antitumor immune responses and overcoming resistance mechanisms. Among these new modalities, antibody-drug conjugates (ADCs), therapeutic cancer vaccines, and adoptive cellular therapies are significantly changing the systemic treatment paradigm in NSCLC. Simultaneously, advances in neoantigen discovery, mRNA vaccine technology, and personalized vaccine design have renewed interest in therapeutic cancer vaccines for generating durable antitumor immune responses. In parallel, adoptive cellular immunotherapies, such as chimeric antigen receptor (CAR)-T cells, natural killer (NK)-cells, and tumor-infiltrating lymphocytes (TILs) are growing as effective approaches to improve immune-mediated tumor eradication in NSCLC. This manuscript summarizes the recent developments of these next-generation precision immuno-oncology platforms, highlighting their working mechanisms, progress in translation, and clinical use. It also explores strategies for combinational therapy, predictive biomarkers, inhibitors of tumor microenvironment modulation, and mechanisms of resistance in the context of therapeutic efficacy and patient selection. Collectively, these developing immunotherapeutic platforms as a whole constitute a brighter paradigm for more personalized and effective systemic treatment approaches in NSCLC.