Personalised cancer vaccines: the next frontier or an elusive goal?

While the concept of cancer vaccines – which aim to eliminate tumour cells by inducing an immune response against specific immune determinants present on the surface of tumour cells – has existed for decades, the development of clinically effective vaccine approaches has proved challenging. A one-size-fits-all approach to cancer immunotherapy has demonstrated to be ineffective due to the high molecular heterogeneity amongst tumours (Curr Opin Pharmacol. 2013 Aug;13(4):497-503), and tumour-specific neoantigens differ from individual to individual. Moreover, tumour heterogeneity is the fuel of clonal evolution and drives therapeutic resistance. So, a personalised approach to treatment that raises immunity against multiple targets is required but has not been feasible in the past due to the extremely high labour and resource needs of devising such an approach.

In the past decade, next-generation sequencing (NGS) has enabled thousands of individual cancer genomes to be sequenced at scale, and to determine the mutational profile of a single tumour and thus identify the cancer mutations that have the potential to generate neoantigens. Ultimately, this has led to the development of genomics-guided personalised cancer vaccines (PCV) (summarised in Cancer Discov. 2025;15:1315–1324) that have demonstrated long-term, tumour-specific immune responses in early clinical studies. A PCV targeting up to 20 predicted personal tumour neoantigens was first evaluated in a study of 6 patients with melanoma in 2017; 4 experienced no recurrence at 25 months post-vaccination, and the remaining 2 patients had recurrent disease but experienced complete tumour regression following subsequent anti-PD-1 therapy (Nature. 2017;547:217–221). At the time of subsequent reporting (Nat Med. 2021;27:515–525), all patients were alive, off therapy and doing well.

Tumour-specific immune responses following neoantigen-targeting vaccines have since been demonstrated in early-phase studies, with and without immune checkpoint inhibitors, across a wide range of malignancies, including glioblastoma, kidney, ovarian, lung and bladder cancers. Despite the promises, positive findings have been reported in only very small pilot populations.

This is a pivotal time for cancer vaccines research: a series of large-scale, industry-sponsored randomised clinical trials are currently evaluating PCVs in several solid tumours. The first data are anticipated in the next 1–2 years as the culmination of large collaborative efforts over recent years. Ongoing industry-sponsored PCV trials include an adjuvant phase II trial with and without pembrolizumab for patients with high-risk melanoma (KEYNOTE-942), a frontline study in patients with kidney cancer, and adjuvant trials in patients with bladder cancer and non-small cell lung cancer. It remains to be seen whether results from these studies will be practice-changing.

Beyond the present time, a key necessity will be the integration of tumour genomic characterisation as part of routine clinical diagnostic testing for cancer. A reduction in turnaround times for genomic results and the overall time it takes for patients to receive the vaccine from diagnosis will also be a major focus for cancer vaccine manufacturers. Given the challenges of coordinating the many aspects of vaccine manufacture, partnering with industry hopefully will provide the resources required to develop processes at scale and to streamline time, costs and labour.