Abstract PR021: A cancer vaccine for de novo metastatic prostate cancer: learning patients stratification from the UV1 trial

Abstract Human telomerase reverse transcriptase (hTERT) vaccine has been found to be safe for de novo metastatic (M1) prostate cancer patients in a phase 1/2a clinical study. Patients experiencing early immune response to the vaccine had an extraordinary favorable 10-year survival rate. Nevertheless, the mechanisms behind the immune response induced by the hTERT peptide vaccine are not investigated and understanding these mechanisms means designing better peptides, better trials and with companion biomarkers for patients stratification. The patients cohort is composed of 21 patients treated with androgen deprivation therapy, radiotherapy, and hTERT peptide vaccine. We used RNA-sequencing and TCR-sequencing (20 and 14 pre-treatment and 20 and 21 post-treatment specimens, respectively) to inspect the changes in transcriptome and TCR-repertoire after the hTERT vaccine treatment and differences between patients that had early immune response and patients that had late or no response. We found multiple hallmarks being shifted after the treatment and being different between early and late responders. Also, a change in activity of multiple gene set signatures was detected after the treatment and activity of part of the gene set signatures predicted survival. Deconvolution of cell type composition from RNA-sequencing data revealed changes in immune cell abundances after the treatment. TCR-sequencing revealed changes in composition and diversity of TCR repertoires after the treatment both in the prostate and from patietnts’ blood, and these differed between early and late responders. The results of this study will help to predict patients’ responses to the cancer vaccines and to further understand the mechanisms behind successful therapeutic combinations. Citation Format: Reetta Nätkin, Eirik Høye, Wolfgang Lilleby, Nikolai Engedal, Julia Elisabeth. Simensen, Espen Basmo. Ellingsen, Marita Westhrin, Ingunn Westgaard, Eivind Hovig, Matti Nykter, Alfonso Urbanucci. A cancer vaccine for de novo metastatic prostate cancer: learning patients stratification from the UV1 trial [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Innovations in Prostate Cancer Research and Treatment; 2026 Jan 20-22; Philadelphia PA. Philadelphia (PA): AACR; Cancer Res 2026;86(2_Suppl):Abstract nr PR021.