Nanomedicine-Enhanced CAR-Engineered Immunotherapy for Lung Cancer: Focusing on Multimodal Strategies and Precision Therapy

Lung cancer remains a major therapeutic challenge because of its molecular and antigenic heterogeneity, rapid evolution, treatment resistance, and immunosuppressive tumor microenvironment (TME). Although chimeric antigen receptor T-cell (CAR-T) therapy has transformed the treatment of hematological malignancies, its efficacy in lung cancer remains constrained by antigen heterogeneity, poor tumor trafficking and infiltration, T-cell dysfunction, suppressive stromal and myeloid compartments, manufacturing complexity, and pulmonary on-target off-tumor toxicity. Nanomedicine offers a versatile platform to address these barriers by improving CAR-T manufacturing and functional fitness, enabling targeted delivery of nucleic acids and immunomodulators, remodeling the TME, enhancing local accumulation and controlled activation, and supporting transient in situ generation of CAR-engineered immune cells. This review integrates these advances within a Route-Antigen-Microenvironment-Programming (RAMP) framework and emphasizes the mechanistic interdependence among delivery route, target selection, local tumor ecology, and CAR generation and control. We examine the antigen landscapes of non-small-cell and small-cell lung cancer and propose a quantitative framework for antigen selection that incorporates antigen density, spatial and temporal heterogeneity, normal-tissue safety, and engineering compensability. We further discuss nanotechnology-assisted manufacturing, cell-surface nanobackpacks, tumor preconditioning, local biomaterial reservoirs, in vivo CAR programming, pulmonary delivery, multimodal therapy, and theranostic monitoring. Most nano-enabled approaches are still supported primarily by preclinical studies or evidence from non-lung-cancer settings, underscoring the need for standardized assessment of biodistribution, reproducibility, immunogenicity, pulmonary safety, and long-term material fate. Integrating quantitative antigen profiling with biodegradable and controllable materials and lung-relevant translational models may help advance CAR-engineered immunotherapy toward a spatially controlled, dynamically monitored, and personalized therapeutic platform for lung cancer.

Abstract from PubMed Central (PMID 43022662, PMC13757427). This entry was added automatically by our daily literature monitor because it matches the topics we follow; read the full paper at the original source.