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Neoantigen targeted dendritic cell vaccine generates durable T cell responses exhibiting the full spectrum of differentiation states in NSCLC patients

ABSTRACT: Background. Dendritic cell (DC)-based neoantigen vaccination holds potential as a safe and effective adjuvant therapy for patients with early-stage, resectable NSCLC, a tumor type typically characterized by high mutational loads. DCs have the unique ability to elicit robust antitumoral T-cell responses, while neoantigens are ideal targets to elicit high-affinity T cell responses with exquisite tumor specificity. Here, we present the results of a phase I clinical trial in which a novel DC vaccine targeting neoantigens was evaluated in six patients with early stage, resected NSCLC. Methods. Tumor samples were subjected to a comprehensive neoantigen identification approach encompassing genomics, transcriptomics and immunopeptidomics. Patients underwent leukapheresis for the manufacturing of monocyte-derived DCs loaded with neoantigens (Neo-mDCs) according to a four-day protocol. Neo-mDCs were injected intravenously following an intrapatient dose escalation scheme. Primary endpoint of the trial was safety. Secondary endpoints were feasibility, immunogenicity, and relapse-free survival. As a quality control, dendritic cells transfected with the mRNA-encoded neoantigen were analyzed by shotgun proteomics to validate expression of the mRNA-encoded neoantigen. Results. The vaccine was demonstrated to be feasible and safe. T cell responses were observed in 5 of 6 vaccinated patients and were dominated by CD8+ T cells, which could be detected ex vivo at high frequencies >1.5 years after the last dose. Furthermore, single cell analysis indicated that the CD8+ T cell responsive population was polyclonal and exhibited the near entire spectrum of T cell differentiation states, including a naïve-like state associated with long lasting memory. Additionally, mRNA-encoded neoantigen were detected by shotgun proteomics in four patients out of the six patients that were tested.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Dendritic Cell

DISEASE(S): Non-small Cell Lung Carcinoma

SUBMITTER: Fabien Thery

LAB HEAD: Prof. Francis Impens

PROVIDER: PXD044799 | Pride | 2024-03-17

REPOSITORIES: Pride

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			Action	DRS
	2022_07.fasta	Fasta
	B07915_Ap_WNE1_CMB-719_FRIMP-Rupert_shotgun-MIDRIXNEO_180803_rep1.raw	Raw
	B07925_Ap_WNE1_CMB-719_FRIMP-Rupert_shotgun-MIDRIXNEO_180803_rep2.raw	Raw
	B07935_Ap_WNE1_CMB-719_FRIMP-Rupert_shotgun-MIDRIXNEO_180803_rep3.raw	Raw
	B102432_Bp_110uPac2942_CMB-1064_FRIMP_Fabien_shotgun-1.raw	Raw

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Neoantigen targeted dendritic cell vaccine generates durable T cell responses exhibiting the full spectrum of differentiation states in NSCLC patients

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