Are therapeutic cancer vaccines genuine game changers?

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Our immune systems engage in perpetual trials of strength against malignancies, with our health — and even our lives — being the ultimate prize.

Unfortunately, the immune system does not always come out on top. Cancers mutate as they grow, which creates colonies of heterogenous cells that vary in fitness. Some cells, for instance, are treatment-resistant or evade the immune system. This diversity is one reason why cancer prognosis is notoriously unpredictable.¹

The pendulum can, however, swing the other way. For example, the immune system eliminates many precancerous cells before they transform into malignancies.²

On the other hand, if they avoid elimination, cancers mutate and produce a repertoire of neoantigens: new proteins that stimulate immune responses. Thus, the immune system may renew its attack. The neoantigens also offer a target for therapeutic cancer vaccines (TCVs), which bolster the immune response and thus treat the malignancy.³ But are these vaccines really the ‘game changers’ heralded in some headlines?

Right timing

In some ways, TCVs are treatments whose time has come. During the late 19th and early 20th century, William Coley, a New York surgeon, used a bacterial vaccine to induce robust immune responses in patients with inoperable sarcomas (malignancies in soft tissues or bones).

Coley achieved a cure rate of better than 10 per cent.⁴ But rapid advances in chemotherapy and other cancer treatments, some of which target critical steps in immune pathways, meant that using vaccines to treat rather than prevent cancers fell by the wayside.

Recently, however, a confluence of trends has renewed interest in TCVs. For example, the immunisation programmes against SARS-CoV-2 show that updating mRNA vaccines is now relatively easy. Oncologists are also using cancer vaccines in new ways to reduce the likelihood of disease recurrence, while researchers have gained unprecedented understanding of cancer genetics and shifting antigen patterns. Indeed, TCVs can be personalised to target the unique abnormalities in an individual malignancy.⁵

For example, patients with stage III or IV clear cell renal cell carcinoma (CCRCC) usually undergo surgery. They may also receive pembrolizumab, an immune checkpoint inhibitor, another mechanism that induces anticancer immune responses. Nevertheless, about two-thirds of CCRCCs recur.

A recent study assessed personalised vaccines in nine people with stage III or IV CCRCC. After surgery, patients received the vaccine to mop up remaining cancer cells. Predictive algorithms suggested the neoantigens targeted by each patient’s TCV.⁶ “We pick targets that are unique to the cancer and different from any normal part of the body, so the immune system can be effectively ‘steered’ towards the cancer in a very specific way,” says study author David Braun of the Yale Cancer Centre in the US.

T-lymphocytes, a type of white blood cell, attack and destroy cancerous and pre-malignant cells. In this study, within three weeks, the number of vaccine-induced T-cells increased by a mean of 166-fold. These T-cells persisted at high levels for up to three years. Some patients experienced injection site reactions and flu-like symptoms, but all remained cancer-free after, on average, 34.7 months. Clinical trials are needed to confirm these promising early results.⁶

Off the shelf

Cancer vaccines can also be fixed: patients receive the same vaccine, which offers the benefits of mass production.⁵ For instance, when untreated, approximately one-third of grade 3 cervical intraepithelial neoplasias (CIN3) progress to cervical cancer within 10 years and about half do the same in 30 years. The Vvax001 vaccine uses Semliki Forest virus to deliver an immune-stimulating payload.

Mosquitos spread Semliki Forest virus, which is endemic across parts of Africa. Vvax001 uses a modified Semliki Forest virus that cannot replicate but produces two proteins (E6 and E7) that are expressed only by cells infected with human papillomavirus type 16 (HPV16), a leading cause of CIN and cervical cancer.⁷

Eighteen patients with HPV16-positive CIN3 received three doses of Vvax001 three weeks apart. Patients were monitored before a final biopsy 19 weeks after immunisation. At the end of the study, lesions were significantly smaller in 17 patients. Smaller lesions were evident a month after the third vaccination. Three patients showed complete regressions, while six regressed to low-grade dysplasia.

The nine patients whose disease did not regress underwent loop excision surgery. Researchers found no residual disease in four patients, so waiting longer before surgery may have eradicated the CIN3. No patient had a recurrence during a median follow-up of 20 months.⁷

“To the best of our knowledge, this response rate makes Vvax001 one of the most effective therapeutic vaccines for HPV16-associated CIN3 lesions reported to date,” says principal investigator Refika Yigit, oncological gynaecologist at the University Medical Centre Groningen, Netherlands. “If confirmed in a larger trial, our results could mean that at least half of the patients with CIN3 might be able to omit surgery, and avoid all of its possible side-effects and complications.”

On the launch pad

More than a century after Coley’s pioneering research, TCVs are beginning to move from the bench to the cancer ward. But realising their potential needs concerted effort from funders, governments and researchers.

A paper published online by Cambridge University Press in January suggests using lessons from the SARS-CoV-2 pandemic to drive research into cancer vaccines.⁵ “Processes were streamlined, pragmatism prevailed over perfections and groups were able to make timely decisions,” the authors remark. “Cancer vaccine trials should be delivered in a similar fashion.”

They add that the NHS, drug companies, triallists and other stakeholders should create ‘shared missions’ to deliver continual iterative improvement of cancer vaccine technologies.

In addition, they call for more investment in trial infrastructure and better public awareness about, for example, the potential opportunities and limitations of cancer vaccines.

Against this background, the NHS Cancer Vaccine Launch Pad aims to speed access to clinical trials of mRNA personalised cancer vaccines. The scheme allows cancer patients receiving NHS treatment in England to be assessed for eligibility to join a cancer vaccine clinical trial. The NHS says it will increase access in an equitable way and aims to provide up to 10,000 patients with personalised cancer treatments by 2030.

Lennard Lee, associate professor of cancer vaccines at the University of Oxford and clinical adviser to the Cancer Vaccine Launch Pad, says: “A central challenge in developing cancer vaccines lies in harnessing national infrastructure, particularly the healthcare system, to facilitate efficient trials. This requires careful coordination and allocation of resources to support local trial delivery centres across the country. Yet the UK is a scientific powerhouse – meaning that with continued investment and effort, there is no reason why the [country] shouldn’t be a pioneer in cancer vaccine development.”

References

1. Nature Reviews Cancer 2024; 24:718-733
2. BMC Medicine 2016; 14:73
3. Frontiers in Immunology 2021; Apr 16; 12:672356
4. Pharmacology & Therapeutics 1994; 64:529-64
5. Cambridge Prisms: Precision Medicine 2025; 3:e1
6. Nature 2025; DOI:10.1038/s41586-024-08507-5
7. Clinical Cancer Research 2025; DOI: 10.1158/1078-0432.Ccr-24-1662