Assessment of Immune Response Following Dendritic Cell-Based Immunotherapy in Pediatric Patients With Relapsing Sarcoma

Frontiers in Oncology

Zdenek Rehak²  Dasa Cerna³  Eva Hlavackova³  Peter Mudry³  Pavel Mazanek³  Zdenek Pavelka³  Lucie Faberova³  Jana Merhautova⁴  Jaroslav Sterba⁵  Iveta Selingerova⁶  Lenka Zdrazilova-Dubska⁶  Lenka Fedorova⁶  Katerina Pilatova⁶  Dalibor Valik⁶  Regina Demlova⁶ 

[1] Department of Laboratory Medicine, Masaryk Memorial Cancer Institute, Brno, Czechia;Department of Nuclear Medicine, Masaryk Memorial Cancer Institute, Brno, Czechia;Department of Pediatric Oncology, University Hospital and Faculty of Medicine, Masaryk University, Brno, Czechia;Department of Pharmacology, Faculty of Medicine, Masaryk University, Brno, Czechia;International Clinical Research Center, St. Anne's University Hospital, Brno, Czechia;Regional Centre for Applied Molecular Oncology, Masaryk Memorial Cancer Institute, Brno, Czechia;

关键词: dendritic cells;    anticancer immunotherapy;    dendritic-cell (DC)-based vaccine;    pediatric sarcoma;    academic clinical trials;    immunomonitoring;   

DOI  :  10.3389/fonc.2019.01169

来源: DOAJ

【 摘 要 】

Monocyte-derived dendritic cell (DC)-based vaccines loaded with tumor self-antigens represent a novel approach in anticancer therapy. We evaluated DC-based anticancer immunotherapy (ITx) in an academic Phase I/II clinical trial for children, adolescent, and young adults with progressive, recurrent, or primarily metastatic high-risk tumors. The primary endpoint was safety of intradermal administration of manufactured DCs. Here, we focused on relapsing high-risk sarcoma subgroup representing a major diagnosis in DC clinical trial. As a part of peripheral blood immunomonitoring, we evaluated quantitative association between basic cell-based immune parameters. Furthermore, we describe the pattern of these parameters and their time-dependent variations during the DC vaccination in the peripheral blood immunograms. The peripheral blood immunograms revealed distinct patterns in particular patients in the study group. As a functional testing, we evaluated immune response of patient T-cells to the tumor antigens presented by DCs in the autoMLR proliferation assay. This analysis was performed with T-cells obtained prior to DC ITx initiation and with T-cells collected after the fifth dose of DCs, demonstrating that the anticancer DC-based vaccine stimulates a preexisting immune response against self-tumor antigens. Finally, we present clinical and immunological findings in a Ewing's sarcoma patient with an interesting clinical course. Prior to DC therapy, we observed prevailing CD8+ T-cell stimulation and low immunosuppressive monocytic myeloid-derived suppressor cells (M-MDSC) and regulatory T-cells (Tregs). This patient was subsequently treated with 19 doses of DCs and experienced substantial regression of metastatic lesions after second disease relapse and was further rechallenged with DCs. In this patient, functional ex vivo testing of autologous T-cell activation by manufactured DC medicinal product during the course of DC ITx revealed that personalized anticancer DC-based vaccine stimulates a preexisting immune response against self-tumor antigens and that the T-cell reactivity persisted for the period without DC treatment and was further boosted by DC rechallenge.Trial Registration Number: EudraCT 2014-003388-39.

【 授权许可】

Unknown