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Clinical Study of Personalized mRNA Vaccine Encoding Neoantigen in Patients With Advanced Digestive System Neoplasms

ABSTRACT: A single arm, open-label pilot study is designed to determine the safety, tolerability and effectiveness of personalized mRNA tumor vaccine encoding neoantigen in Patients with advanced esophageal squamous carcinoma, gastric adenocarcinoma, pancreatic adenocarcinoma and colorectal adenocarcinoma

DISEASE(S): Adenocarcinoma,Carcinoma, Squamous Cell,Colorectal Adenocarcinoma,Gastric Adenocarcinoma,Pancreatic Adenocarcinoma,Carcinoma,Advanced Esophageal Squamous Carcinoma

PROVIDER: 2268561 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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The CD155/TIGIT axis promotes and maintains immune evasion in neoantigen-expressing pancreatic cancer

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Personalized neoantigen peptide vaccine for advanced solid cancer

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Personalized NeoAntigen Cancer Vaccine with RT for Newly Diagnosed Glioblastoma

Project description:Personalized NeoAntigen Cancer Vaccine with RT for Newly Diagnosed Glioblastoma

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Adenoviral based-vaccine promotes neoantigen specific CD8+ T cell stemness and tumor rejection

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

Project description: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.

2024-03-17 | PXD044799 | Pride

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