Two personalized cancer vaccination strategies are shown to be safe and to provide clinical benefit to patients with high-risk melanoma in small-scale human trials reported in two separate papers published online in Nature this week. The findings demonstrate the clinical feasibility and safety of vaccines tailored to patients’ individual cancer mutations, and could inform strategies to develop personalized cancer immunotherapy treatments.
Developing effective cancer treatments that destroy tumour cells without damaging healthy cells has long remained a challenge. Cancer immunotherapy approaches, which mobilize a patient’s immune system to specifically target cancer cells, have shown promise, but each patient’s tumour has a unique set of mutations that must first be identified, which necessitates individually tailored vaccines.
Catherine Wu and colleagues report results of a phase I clinical trial of a cancer vaccine that targets up to 20 personalized tumour neo-antigens (targets for an anti-tumour immune response). They found that the vaccine was safe and induced antigen-specific immune responses in the participants. Four of the six patients treated with the vaccine showed no recurrence at 25 months, while the other two participants, with progressive forms of melanoma, were later treated with another type of so-called ‘checkpoint therapy’ (anti-PD-1 therapy) and underwent complete tumour regression.
In a separate paper, Ugur Sahin and co-authors report the first-in-human application of a personalized RNA-based vaccine approach, which targets cancer antigens called neo-epitopes, in 13 patients with melanoma. In all patients, the authors show that the vaccine boosts immunity against some of the patients’ specific tumour antigens, and in two patients, infiltration of vaccine-induced T cells into tumours was observed. Eight of the 13 patients remained tumour-free at 23 months. Five patients had tumour relapses before starting neo-epitope vaccination. Two of these patients experienced objective responses after neo-epitope vaccination and one patient experienced a complete tumour regression response after sequential administration of neoepitope vaccination and of anti-PD-1 therapy.
“Controlled, randomized phase II clinical trials with more participants are now needed to establish the efficacy of these vaccines in patients with any type of cancer that has enough mutations to provide sufficient neoantigen targets to enable this type of approach” concludes Cornelius Melief in an accompanying News & Views article.
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