Abstract
An RNA vaccine against nonmutated, shared tumor antigens promoted T-cell responses in melanoma.
Major Finding: An RNA vaccine against nonmutated, shared tumor antigens promoted T-cell responses in melanoma.
Concept: This phase I trial revealed promising early efficacy results and possible synergy with PD-1 blockade.
Impact: This vaccine and others targeting nonmutated shared antigens continue to be of interest in melanoma.
Immune-checkpoint blockade has revolutionized the treatment of melanoma, but it is not always effective, highlighting the need for therapies that enhance the response to these treatments. One strategy could be to stimulate the antitumor immune response using a vaccine such as FixVac, an intravenously administered liposomal RNA vaccine currently under development that contains RNA that is optimized for translation in immature dendritic cells and encodes four nonmutated, shared tumor-specific antigens. Sahin and colleagues report the results of an interim exploratory analysis from the first-in-human, phase I dose-escalation trial of FixVac alone or in combination with anti–PD-1 in patients with stage IIIB, IIIC, or IV melanoma. In 50 patients, the IFNγ-ELISpot assay (which typically reflects only high-magnitude T-cell responses) indicated immune responses against at least one of the antigens in more than 75% of patients; in 20 patients, the commonly used post–in vitro stimulation IFNγ-ELISpot assay detected immune responses against at least one of the antigens in 100% of patients. Additionally, antigen-specific CD8+ T cells increased over four to eight weeks to represent high single-digit to low double-digit percentages of circulating CD8+ T cells, and memory T cells persisted for more than one year with monthly maintenance vaccination or for several months without continuous vaccination. An exploratory analysis of clinical activity in 42 patients—41 of whom had stage IV disease that had previously been treated with immune checkpoint blockade—revealed that partial response or stable disease was the best outcome in 12% or 28%, respectively, of the 25 patients treated with FixVac monotherapy, and partial response was the best outcome in 35% of the 17 patients in the combination-therapy group. Notably, the patients exhibiting partial responses tended to be the ones with the most diversified, highest-magnitude T-cell responses, although a potential confounder is that these patients stayed on the trial longer for sample collection. In summary, this interim analysis shows that FixVac shows promising early signs of efficacy and may synergize with PD-1 blockade.
Note: Research Watch is written by Cancer Discovery editorial staff. Readers are encouraged to consult the original articles for full details. For more Research Watch, visit Cancer Discovery online at http://cancerdiscovery.aacrjournals.org/CDNews.
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