by ecancer reporter Kate Turton

Personalised anti-cancer vaccines are a safe and effective way to treat cancer, according to two separate clinical trials published in Nature this week.

These studies provide the first demonstration in human patients of the clinical safety and feasibility of individually-tailored vaccines for treating high-risk melanoma, and pave the way towards personalised immunotherapy.

Research teams in the USA and Europe have shown that vaccines can generate a strong immune response against cancer, allowing the body to identify and destroy tumours whilst leaving healthy tissues intact.

This ability to specifically target tumour cells and avoid normal cells has long been a major challenge in the design of effective cancer immunotherapies.

DNA mutations within tumour cells create neo-antigens, which differentiate them from healthy cells.

Neo-antigens can therefore be exploited as markers that the immune system can use to seek out and destroy tumour cells in the body.

The body can spontaneously detect neo-antigens and mount an immune response but the process is inefficient.

Immunotherapies attempt to mobilise the immune system to respond to neo-antigens with greater speed and specificity than the natural process.

However, because each tumour has its own unique set of neo-antigens, a personalised vaccine must be created for each individual patient.

Vaccines developed by Catherine Wu and colleagues in Massachusetts, USA, were used to target up to 20 neo-antigens per tumour.

Six patients took part in a trial to test the safety and effectiveness of these vaccines: four showed no recurrence of melanoma after two years; the remaining two (who also had another form of cancer) responded to the vaccines and exhibited tumour regression after treatment with an additional therapy.

The authors report that all six patients experienced safe levels of immune response, with only minor side-effects to the vaccines (such as mild flu-like symptoms, injection site reactions, rash and fatigue).

According to the authors, this study demonstrates that personal neo-antigen vaccination strategies are safe, feasible and able to produce strong immune reponses in a clinical setting.

Furthermore, they report that the vaccines generate a greater immune response than that induced by existing immunotherapies.

Meanwhile the European team, led by Ugur Sahin, tested the effectiveness of individualised RNA-based vaccines in thirteen melanoma patients.

Participants in this clinical trial had a recent history of disease and a high risk of relapse.

They developed immune responses against neo-epitopes on tumour antigens, with no serious side effects to their vaccinations.

Eight of the patients showed no recurrence of cancer over two years.

The remaining five experienced relapse during the study and whilst they responded to the vaccines, they also received additional therapies.

“Our study demonstrates the clinical feasibility, safety and antitumour activity of targeting individual cancer mutations by RNA neo-epitope vaccines” Sahin’s team reports.

Taken together, the results of these two trials support the case for developing individually-tailored medicines for a wider range of cancer patients.

The studies may have involved small numbers of participants but they provide proof-of-principle for the use of personalised vaccines to generate highly specific immune responses against tumour cells.

The next step will be to carry out controlled, randomised phase II clinical trials involving greater numbers of participants to establish the efficacy of personalised vaccines in patients with other forms of cancer.

“Future vaccine trials will take advantage of improved methods for predicting antigen presentation to increase the fraction of neo-antigens inducing tumour-reactive T cells and will test for synergy with checkpoint blockade and other immunotherapeutics” say Wu and colleagues.

References

Sahin, U. et al. Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer. Nature. July 5, 2017. doi:10.1038/nature23003

Ott, P.A. et al. An immunogenic personal neoantigen vaccine for patients with melanoma. Nature. July 5, 2017. doi:10.1038/nature22991