RT Journal Article SR Electronic T1 Durable and dynamic hTERT immune responses following vaccination with the long-peptide cancer vaccine UV1: long-term follow-up of three phase I clinical trials JF Journal for ImmunoTherapy of Cancer JO J Immunother Cancer FD BMJ Publishing Group Ltd SP e004345 DO 10.1136/jitc-2021-004345 VO 10 IS 5 A1 Ellingsen, Espen Basmo A1 Aamdal, Elin A1 Guren, Tormod A1 Lilleby, Wolfgang A1 Brunsvig, Paal F A1 Mangsbo, Sara M A1 Aamdal, Steinar A1 Hovig, Eivind A1 Mensali, Nadia A1 Gaudernack, Gustav A1 Inderberg, Else Marit YR 2022 UL http://jitc.bmj.com/content/10/5/e004345.abstract AB Background Therapeutic cancer vaccines represent a promising approach to improve clinical outcomes with immune checkpoint inhibition. UV1 is a second generation telomerase-targeting therapeutic cancer vaccine being investigated across multiple indications. Although telomerase is a near-universal tumor target, different treatment combinations applied across indications may affect the induced immune response. Three phase I/IIa clinical trials covering malignant melanoma, non-small cell lung cancer, and prostate cancer have been completed, with patients in follow-up for up to 8 years.Methods 52 patients were enrolled across the three trials. UV1 was given as monotherapy in the lung cancer trial and concurrent with combined androgen blockade in the prostate cancer trial. In the melanoma study, patients initiated ipilimumab treatment 1 week after the first vaccine dose. Patients were followed for UV1-specific immune responses at frequent intervals during vaccination, and every 6 months for up to 8 years in a follow-up period. Phenotypic and functional characterizations were performed on patient-derived vaccine-specific T cell responses.Results In total, 78.4% of treated patients mounted a measurable vaccine-induced T cell response in blood. The immune responses in the malignant melanoma trial, where UV1 was combined with ipilimumab, occurred more rapidly and frequently than in the lung and prostate cancer trials. In several patients, immune responses peaked years after their last vaccination. An in-depth characterization of the immune responses revealed polyfunctional CD4+ T cells producing interferon-γ and tumor necrosis factor-α on interaction with their antigen.Conclusion Long-term immunomonitoring of patients showed highly dynamic and persistent telomerase peptide-specific immune responses lasting up to 7.5 years after the initial vaccination, suggesting a plausible functional role of these T cells in long-term survivors. The superior immune response kinetics observed in the melanoma study substantiate the rationale for future combinatorial treatment strategies with UV1 vaccination and checkpoint inhibition for rapid and frequent induction of anti-telomerase immune responses in patients with cancer.Data are available upon reasonable request. Relevant data are provided in the publication and online supplementary material. Further details are available upon reasonable request.