Abstract B119: A DNA plasmid melanoma cancer vaccine, SCIB1, combined with nivolumab + ipilimumab induces functional CD4 and CD8 T cell responses in patients with advanced unresectable melanoma

Abstract Background: Targeting melanoma by T cells drives anti-tumour responses. Previously in a phase 1/2 study we successfully evaluated a DNA vaccine, SCIB1, incorporating CD8 and CD4 T cell epitopes from TRP-2/gp100 into an antibody framework to allow Fc targeting of activated dendritic cells. In stage 3/4 unresectable melanoma patients receiving SCIB1 as a monotherapy we showed a 60% disease control rate (DCR) and 88% of patients treated with SCIB1 post tumour resection remained disease free for 5 years. Checkpoint inhibitor (CPI) therapies are now standard of care for melanoma, with nivolumab and ipilimumab being the most used combination. The current Phase 2 SCOPE trial tests the hypothesis that unresectable patients may have an improved response when SCIB1 is combined with CPI. In patients enrolled in this trial, the induction of SCIB1 specific T cell responses is also being evaluated. Methods: Patients were treated with nivolumab, ipilimumab and SCIB1 (8mg) i.m. using needle-free injection at a fixed dosing schedule for a total of 10 doses over 24 months. CPI therapy was administered i.v. in accordance with their respective SmPC. Vaccine specific T cell responses to SCIB1 were assessed via a combination of IFNγ ELISpot, single-cell RNA- & TCR-seq and TCR repertoire analysis. Results: From 41 patients enrolled in the SCOPE study, we will present data on functional T cell responses to the TRP2 and gp100 peptides incorporated within SCIB1. Characterization of these T cell responses showed SCIB1 induces both CD4 and CD8 mediated responses. For three patients, we have isolated CD8 TCRs which are reactive to the SCIB1 epitopes incorporated in the vaccine. Single-cell RNA- & TCR-seq was performed on sorted CD8+ IFNγ+ cells with RNA-seq analysis revealing several expanded TCR clonotypes in CD8 T cell populations with a cytotoxic transcriptional profile. Using Lentivirus-TCR transduced T cells we have successfully shown that six isolated CD8 TCRs react specifically to the TRP-2 or gp100 epitopes incorporated into SCIB1. We have characterized the T cell responses and have mapped the minimal epitope and the presenting HLA allele. Bulk TCR repertoire sequencing revealed that, in two out of three patients, the isolated SCIB1 specific TCRs were undetectable in peripheral CD8 T cells collected from pre-vaccination samples. The same TCRs were detectable in the post-vaccination CD8 TCR repertoire. Conclusions: SCIB1 in combination with nivolumab and ipilimumab consistently induced functional CD4 and CD8 T cell responses, with demonstratable vaccine induced expansion of SCIB1 specific TCR clonotypes. Citation Format: Joseph Chadwick, Gaëlle Cane, Sabaria Shah, Katie Mann, Patrick Copeland, Daisy Weston, Jordan Wright, Leanne Toon, Heather Shaw, Poulam Patel, Miranda Payne, Satish Kumar, Sarah Danson, Martin Highley, Clare Barlow, Kellati Prasad, Ioannis Karydis, Maria Marples, Kate Young, Pippa Corrie, Robert Miller, Rachael Metheringham, Georgia Goodhew, Nermeen Varawalla, Samantha Paston, Lindy Durrant. A DNA plasmid melanoma cancer vaccine, SCIB1, combined with nivolumab + ipilimumab induces functional CD4 and CD8 T cell responses in patients with advanced unresectable melanoma [abstract]. In: Proceedings of the AACR IO Conference: Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2025 Feb 23-26; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2025;13(2 Suppl):Abstract nr B119.