J 2019

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

FĚDOROVÁ, Lenka, Peter MÚDRY, Kateřina PILÁTOVÁ, Iveta SELINGEROVA, Jana MERHAUTOVÁ et. al.

Basic information

Original name

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

Authors

FĚDOROVÁ, Lenka (203 Czech Republic, belonging to the institution), Peter MÚDRY (203 Czech Republic, belonging to the institution), Kateřina PILÁTOVÁ (203 Czech Republic, belonging to the institution), Iveta SELINGEROVA (203 Czech Republic), Jana MERHAUTOVÁ (203 Czech Republic, belonging to the institution), Zdenek REHAK (203 Czech Republic), Dalibor VALÍK (203 Czech Republic, belonging to the institution), Eva HLAVÁČKOVÁ (203 Czech Republic, belonging to the institution), Dáša ČERNÁ (703 Slovakia, belonging to the institution), Lucie FABEROVÁ (203 Czech Republic, belonging to the institution), Pavel MAZÁNEK (203 Czech Republic, belonging to the institution), Zdeněk PAVELKA (203 Czech Republic, belonging to the institution), Regina DEMLOVÁ (203 Czech Republic, belonging to the institution), Jaroslav ŠTĚRBA (203 Czech Republic, belonging to the institution) and Lenka ZDRAŽILOVÁ DUBSKÁ (203 Czech Republic, guarantor, belonging to the institution)

Edition

Frontiers in Oncology, Lausanne, Frontiers Media S.A. 2019, 2234-943X

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30204 Oncology

Country of publisher

Switzerland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

Impact factor

Impact factor: 4.848

RIV identification code

RIV/00216224:14110/19:00111754

Organization unit

Faculty of Medicine

UT WoS

000501248600001

Keywords in English

dendritic cells; anticancer immunotherapy; dendritic-cell (DC)-based vaccine; pediatric sarcoma; academic clinical trials; immunomonitoring; personalized medicine

Tags

International impact, Reviewed
Změněno: 4/3/2020 12:10, Mgr. Tereza Miškechová

Abstract

V originále

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.

Links

LM2015090, research and development project
Name: Český národní uzel Evropské sítě infrastruktur klinického výzkumu (Acronym: CZECRIN)
Investor: Ministry of Education, Youth and Sports of the CR
MUNI/A/1586/2018, interní kód MU
Name: Personalizovaná léčba v dětské onkologii: na cestě k "liquid dynamic medecine" a "N-of-1 clinical trials" (Acronym: Personalizovaná léčba v dětské onkologii)
Investor: Masaryk University, Category A