Abstract 1182: PDC*lung01: An innovative therapeutic cancer vaccine induces specific immune responses in combination with anti- PD-1 treatment in patients with non-small cell lung cancer

Abstract

Abstract We have developed an innovative cancer vaccine for the treatment of advanced NSCLC patients in combination with checkpoint inhibitors. This PDC*lung01 product based on an irradiated plasmacytoid dendritic cell line loaded with HLA-A*02:01 restricted peptides (NY-ESO-1, MAGE-A3, MAGE-A4, Multi-MAGE-A, MUC1, Survivin and Melan-A) is able to prime and expand peptide-specific CD8+ T cells in vitro and in vivo, and is synergistic with anti-Programmed Death (PD)-1 (Plumas et al, 2022; Hannani et al, 2023, NCT03970746). In study PDC-LUNG-101 with EudraCT number 2018-002382-19, PDC*lung01 is injected intravenously and subcutaneously for 6 times at two dose levels, 14 million, or 140 million cells in stage II/IIIA (cohort A1 & A2, monotherapy) or stage IV with TPS≥50% (cohort B1 & B2; in combination with pembrolizumab) patients. We report here the analysis of immune response of 3 cohorts (A1, A2, B1) of patients and the first 19 patients out of 42 (cohort B2) treated with high dose of PDC*lung01 in combination with Pembrolizumab at baseline and 3 timepoints post injection. Several circulating immune parameters have been evaluated at different times before and after vaccination using different assays we have developed: leukocyte count and determination of circulation peptide specific CD8+ T cells by flow cytometry using multimer tools without prior in vitro culture. The assay made on purified CD8+ T-cells allowed us to define a limit of quantification (LOQ) to accurately assess the fold changes of the cell expansion. In addition, tumor microenvironment (TME) was analyzed by multiplex fluorescence immunochemistry. The data of 42 patients for who an immune response has been evaluated (cohorts A and B) will be presented. No major changes in circulating main lymphocyte frequencies (B cells, NK cells, CD4+, CD8+, or Treg T cells) were observed during treatment. In addition, no major cell activation (CD25+, CD54, or DR+) was noted. In contrast, in a significant number of patients, PDC*lung01 induced circulating peptide-specific CD8+ T cell expansion in all 4 cohorts at different levels and time points against at least one out of seven peptides used. The percentages of patients for who an expansion of antigen-specific T-cell were observed were 50%, 64%, 66.7% and 68.4% in A1, A2, B1 and B2 cohorts respectively. The intensity of the immune response was proportional to the dose of PDC*lung01 and to the combination with pembrolizumab. When possible, total and peptide-specific CD8+ T cells were sorted for analysis of TCR repertoire, illustrating the modelling and dynamics of the immune response. The TME features will also be illustrated. To conclude, treatment with PDC*lung01 induces an anti-tumor immune response in a significant number of patients which appears to be enhanced by the combination with pembrolizumab. Citation Format: Joel Plumas, Anne Sibille, Ingel Demedts, Elvire Pons-Tostivint, Charlotte Van de Kerkhove, Sofie Derijcke, Willemijn Theelen, Bonne Biesma, Frank Borm, Els Wauters, Mike Collodoro, Kays Al Badawy, Camille Duchayne, Channa Debruyne, Beatrice Devos, Benoit Colinet, Denis Moro-Sibilot, Maurice Perol, Eva-Lotte Buchmeier, Marcin Skrzypski, Kristof Cuppens, Johan Vansteenkiste. PDC*lung01: An innovative therapeutic cancer vaccine induces specific immune responses in combination with anti- PD-1 treatment in patients with non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1182.