Therapeutic Vaccination in Lung Cancer: Past Attempts, Current Approaches and Future Promises

Abstract

Lung cancer represents a significant burden on global health, necessitating the need for new and effective treatment strategies that expand our current therapeutic repertoire. Immunotherapy, namely immune checkpoint blockade (ICB), has revolutionized lung cancer therapy over the last decade by invigorating anti-tumor T cell responses to prolong survival and quality of life. However, not all patients benefit from ICB, emphasizing the need for novel immunotherapeutic strategies that engage other immune functionalities to offer synergy with already available therapies. There has been a longstanding interest in deploying lung cancer vaccines to generate or enhance tumor antigen-specific T cell responses for greater tumor control. Thus far, success has been limited to early-stage clinical trials, where safety, generation of antigen-specific T cell responses in blood sampling, and some patient benefits have been established. Moving forward, the establishment of widespread clinical success in large-scale trials is a necessity to bring lung cancer vaccines into the therapeutic arsenal. In this review, we examine the logic and mechanisms behind therapeutic lung cancer vaccines, before critically and iteratively examining past and current attempts in lung cancer vaccinology. We also look at early pre-clinical studies and outline the future for therapeutic lung cancer vaccines.

Keywords

Lung cancer / Therapeutic vaccine / Mucosal vaccination

Acknowledgement

Schematics in the manuscript were created with BioRender.com.

Author Contributions

Conceptualization, S.P.Y. and J.S.; Methodology, S.P.Y. and J.S.; Software, S.P.Y.; Validation, S.P.Y.; Formal Analysis, S.P.Y.; Investigation, S.P.Y.; Resources, S.P.Y. and J.S.; Data Curation, S.P.Y.; Writing—Original Draft Preparation, S.P.Y. and J.S.; Writing—Review & Editing, S.P.Y. and J.S., Visualization, S.P.Y.; Supervision, J.S.; Project Administration, S.P.Y. and J.S.; Funding Acquisition, S.P.Y. and J.S.

Ethics Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.

Funding

This research was funded by the US National Institutes of Health grants AI147394, AG069264, AG090337, AG090337, HL170961 and AI176171 to J.S; 5T32CA009109-47 and UVA Comprehensive Cancer Center Trainee Fellowship FY2026 to S.P.Y.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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