After decades of missed promises, cancer vaccines are likely approaching prime time due to major advances in cancer immunobiology, immunotherapy and biomedical technology
The pursuit of cancer vaccines has been one of oncology’s longest and most frustrating journeys. For decades, long before the application of modern immune checkpoint inhibitors, researchers explored the idea of training the immune system to attack molecules expressed by or associated with cancer cells. While the concept is elegant, and important successes have been achieved in preventing transmissible cancers with vaccines against human papillomavirus (HPV) (N Engl J Med. 2020;383:1340–1348) and hepatitis B virus (HBV) (Vaccines (Basel). 2022;10:793), results have been largely disappointing in patients with advanced cancers. Trials using whole-cell vaccines, peptide vaccines, dendritic cell vaccines and related strategies failed to produce tangible benefit, and while modest successes were obtained through the years (N Engl J Med. 2010;363:411–422; N Engl J Med. 2011;364:2119–2127), no cancer vaccine has reached the mainstream of oncology. For many, the field of cancer vaccines became synonymous with disappointment.
Yet, as in other areas of medicine, disruptive progress often comes not from a single breakthrough but from connecting dots across multiple discoveries.
The first dot of this story is the revolution in cancer immunobiology. By showing how immune cells recognise cancer cells (Nat Rev Immunol. 2020;20:651–668), and that immune responses to cancer are constrained by regulatory networks (J Clin Oncol. 2010;28:4531–4538), it became clear that vaccines stimulating responses against individual antigens expressed on cancer cells could not suffice on their own to counteract intratumour immune suppression.
The second dot is pharmacological – i.e., the advent of immune checkpoint inhibitors. By showing that the immune system can naturally mount durable antitumour responses in some patients with cancer once inhibitory signals are lifted (Cell. 2023;186:1652–1669), checkpoint inhibitors were game changers in the success of immunotherapy. If spontaneous immune responses could be reinvigorated, vaccines might provide the missing antigen-specific trigger, or even directly shape immune responses by training the immune system itself to target immune regulatory networks (Semin Immunopathol. 2023;45:253–264S).
The third dot is modern biomedical technology. Advances in sequencing and bioinformatics have made it feasible to identify antigens derived from somatic mutations or neoantigens uniquely expressed in an individual patient’s cancer (Biomark Res. 2025;13:96). The emergence of new immunisation platforms, accelerated by the COVID-19 pandemic, offered rapid and flexible ways to encode these targets into vaccines, while also providing a new rationale for efficient immune stimulation through modern formulations and adjuvants (Cell Mol Immunol. 2025;22:840–868). Today, even personalised cancer vaccines are transitioning from theory to practice (Nat Rev Cancer. 2025;25:517–533).
Still, it is worth remembering that each current vaccine approach bears important limitations. Personalised vaccines present logistical and economic hurdles. Off-the-shelf approaches may lack the precision and patient specificity needed for durable responses. Biomarkers to select the right patients remain underdeveloped. Randomised trials, the ultimate dot that connects innovation to practice, are only now beginning to report results. Finally, vaccines will unlikely be a universal solution, but part of a broader immunotherapy toolkit.
When all the dots are connected, a clear picture emerges: for the first time in decades, cancer vaccines are close to a breakthrough and may soon shed the label of failed promise. Exploiting the low toxicity profile of vaccines compared with other cancer therapies offers opportunities in the whole spectrum of oncology, including early-stage diseases.
This is a pivotal time for cancer vaccines research as many studies are ongoing. Additional dots will arise from future advances at the intersection between basic tumour immunology, biotechnology, and a thoughtful application of artificial intelligence in personalised medicine. Connecting them may finally bring the long-promised breakthrough within the mainstream of clinical oncology.
