Targeted T-cell Immunotherapies for Lung Cancer: Mechanisms, Clinical Applications, and Future Directions

As lung cancer remains one of the most prevalent causes of cancer-related fatalities globally, there continues to be a critical and urgent demand for treatments beyond the current standard of care. This review discusses the current and emerging targeted T-cell immunotherapies for treating lung cancer, as well as how lung tumors cause the development of T cell exhaustion and the corresponding immunotherapies that target these mechanisms. There are currently four major categories of immunotherapies directed toward the activation of T cells: immune checkpoint inhibitors (ICIs), adoptive cell therapies (ACT), bispecific T Cell Engagers (BiTEs), and cancer vaccines. Available clinical trial data are presented for each type of immunotherapy, particularly the clinical trial data for ICIs, demonstrating that these treatments provide an increased survival advantage for patients treated for both Non-Small Cell Lung Cancer (NSCLC) and Small Cell Lung Cancer (SCLC). Remaining clinical challenges include primary or acquired resistance to the immunotherapy, the incidence of immune-related adverse events (irAEs), and the identification of improved predictive biomarkers. Future immunotherapeutic approaches to lung cancer will rely on the use of combination therapy based on sound molecular rationale, the use of personalized neoantigen-based vaccination, the design of next-generation engineered cellular products, and the enhancement of biomarker development to improve therapeutic efficacy and maximize the usage of these innovative therapies.