382 The synthetic long peptide cancer vaccine UV1 in combination with ipilimumab induces a CD4+ Th1 anti-hTERT immune response and an inflammatory tumor microenvironment in patients with melanoma

Background Checkpoint inhibitors (CPIs) have revolutionized the treatment of malignant melanoma. Although melanoma patients may experience deep and durable clinical responses to CPI treatment, majority develop disease progression requiring additional therapy. Combining CPIs with therapeutic cancer vaccines augment anti-tumor immune response thus improve outcomes. UV1 is a vaccine based on synthetic antigens derived from tumor-associated antigen telomerase reverse transcriptase (hTERT). hTERT activated in 85–90% all cancers leads replication telomeric DNA, an essential mechanism for increased proliferation, immortality, invasiveness cells. In this phase I/IIa study combining ipilimumab ( NCT02275416 ), we hypothesized that might provide synergy expansion vaccine-induced T Furthermore, augmented CD4+ Th1 targeting shared tumor increase cell infiltration microenvironment, promoting immune-mediated death. Methods The dynamics were assessed by longitudinal immunomonitoring up 5 years using standard proliferation assay. phenotype functionality cells patient-derived cloning subsequent vitro characterization flow cytometry, peptide stimulation, cytokine release assays. On available biopsies harvested at baseline 12 weeks after initiation, microenvironment was whole-exome sequencing, RNA immunohistochemistry. Results Twelve metastatic enrolled received 9 doses over 20-week period. A persistent (up years) demonstrated 91% evaluable (10/11). Vaccine-specific clones polyfunctional cells, producing both IFN-γ TNF-α upon stimulation. Differential gene expression analysis immunohistochemical showed induction inflammatory ”hot” responders paired biopsies. Conclusions combination robust long-lasting anti-hTERT sculpting local microenvironment. Trial Registration Ethics Approval approved Regional Ethical Committee South East (ID number 25 165). provided their written informed consent participate study.