Journal: Journal of hematology & oncology
This publication is a narrative review on cancer vaccines in lung cancer, focused on overcoming resistance to immune checkpoint inhibitors (ICIs).
Key points:
- ICIs have improved outcomes in lung cancer, but only a subset of patients achieve durable benefit; primary and acquired resistance remain common.
- Resistance is attributed to multiple mechanisms:
- • Poor tumor antigen presentation
- • Impaired T‑cell priming and expansion
- • Physical barriers and an immunosuppressive tumor microenvironment that limit infiltration and function of effector immune cells
- Cancer vaccines are presented as a strategy to:
- • Induce new or boost existing tumor-specific T-cell responses
- • Support long-term immunologic memory
- • Do so with relatively favorable safety
- The review emphasizes:
- • Advances in antigen/neoantigen discovery and prediction
- • Development of both personalized and off‑the‑shelf neoantigen vaccine platforms
- • Personalized vaccines: highly tailored but resource- and time‑intensive
- • Off‑the‑shelf vaccines: more scalable, cheaper, and faster to manufacture, making broader implementation more feasible
- Evidence to date suggests:
- • Vaccines appear more effective in the adjuvant or minimal residual disease setting than in metastatic disease, where high tumor burden and strong immunosuppression limit vaccine effect.
- • Cancer vaccines are generally weak as monotherapy in advanced disease.
- Consequently, current clinical development is moving toward:
- • Combining vaccines with ICIs and other immunotherapies to enhance T-cell activation and function, and to counteract immunosuppressive mechanisms.
- The article synthesizes mechanistic understanding, summarizes ongoing clinical efforts in lung cancer, and outlines future directions for rational vaccine design and combination strategies to address ICI resistance.