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

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.