HLAVÁČKOVÁ, Eva, Kateřina PILÁTOVÁ, Dáša ČERNÁ, Iveta SELINGEROVA, Peter MÚDRY, Pavel MAZÁNEK, Lenka FĚDOROVÁ, Jana MERHAUTOVÁ, Lucie JUREČKOVÁ, Lukáš SEMERÁD, Rita PACASOVA, Lucie FLAJŠAROVÁ, Lenka SOUČKOVÁ, Regina DEMLOVÁ, Jaroslav ŠTĚRBA, Dalibor VALÍK a Lenka ZDRAŽILOVÁ DUBSKÁ. Dendritic Cell-Based Immunotherapy in Advanced Sarcoma and Neuroblastoma Pediatric Patients: Anti-cancer Treatment Preceding Monocyte Harvest Impairs the Immunostimulatory and Antigen-Presenting Behavior of DCs and Manufacturing Process Outcome. Frontiers in Oncology, Lausanne: Frontiers Media S.A., 2019, roč. 9, OCT 25 2019, s. 1-15. ISSN 2234-943X. doi:10.3389/fonc.2019.01034.
Další formáty:   BibTeX LaTeX RIS
Základní údaje
Originální název Dendritic Cell-Based Immunotherapy in Advanced Sarcoma and Neuroblastoma Pediatric Patients: Anti-cancer Treatment Preceding Monocyte Harvest Impairs the Immunostimulatory and Antigen-Presenting Behavior of DCs and Manufacturing Process Outcome
Autoři HLAVÁČKOVÁ, Eva (203 Česká republika, domácí), Kateřina PILÁTOVÁ (203 Česká republika, domácí), Dáša ČERNÁ (703 Slovensko, domácí), Iveta SELINGEROVA (203 Česká republika), Peter MÚDRY (203 Česká republika, domácí), Pavel MAZÁNEK (203 Česká republika, domácí), Lenka FĚDOROVÁ (203 Česká republika, domácí), Jana MERHAUTOVÁ (203 Česká republika, domácí), Lucie JUREČKOVÁ (203 Česká republika, domácí), Lukáš SEMERÁD (203 Česká republika, domácí), Rita PACASOVA (203 Česká republika), Lucie FLAJŠAROVÁ (203 Česká republika, domácí), Lenka SOUČKOVÁ (203 Česká republika, domácí), Regina DEMLOVÁ (203 Česká republika, domácí), Jaroslav ŠTĚRBA (203 Česká republika, domácí), Dalibor VALÍK (203 Česká republika, domácí) a Lenka ZDRAŽILOVÁ DUBSKÁ (203 Česká republika, garant, domácí).
Vydání Frontiers in Oncology, Lausanne, Frontiers Media S.A. 2019, 2234-943X.
Další údaje
Originální jazyk angličtina
Typ výsledku Článek v odborném periodiku
Obor 30204 Oncology
Stát vydavatele Švýcarsko
Utajení není předmětem státního či obchodního tajemství
WWW URL
Impakt faktor Impact factor: 4.848
Kód RIV RIV/00216224:14110/19:00111675
Organizační jednotka Lékařská fakulta
Doi http://dx.doi.org/10.3389/fonc.2019.01034
UT WoS 000496427100001
Klíčová slova anglicky dendritic cells; anti-cancer medications; sarcoma; neuroblastoma; cell-based medicinal products; investigator-initiated clinical trial; manufacturing outcome variability
Štítky 14110321, 14110516, rivok
Příznaky Mezinárodní význam, Recenzováno
Změnil Změnila: Mgr. Tereza Miškechová, učo 341652. Změněno: 4. 3. 2020 12:11.
Anotace
Despite efforts to develop novel treatment strategies, refractory and relapsing sarcoma, and high-risk neuroblastoma continue to have poor prognoses and limited overall survival. Monocyte-derived dendritic cell (DC)-based anti-cancer immunotherapy represents a promising treatment modality in these neoplasias. A DC-based anti-cancer vaccine was evaluated for safety in an academic phase-I/II clinical trial for children, adolescents, and young adults with progressive, recurrent, or primarily metastatic high-risk tumors, mainly sarcomas and neuroblastomas. The DC vaccine was loaded with self-tumor antigens obtained from patient tumor tissue. DC vaccine quality was assessed in terms of DC yield, viability, immunophenotype, production of IL-12 and IL-10, and stimulation of allogenic donor T-cells and autologous T-cells in allo-MLR and auto-MLR, respectively. Here, we show that the outcome of the manufacture of DC-based vaccine is highly variable in terms of both DC yield and DC immunostimulatory properties. In 30% of cases, manufacturing resulted in a product that failed to meet medicinal product specifications and therefore was not released for administration to a patient. Focusing on the isolation of monocytes and the pharmacotherapy preceding monocyte harvest, we show that isolation of monocytes by elutriation is not superior to adherence on plastic in terms of DC yield, viability, or immunostimulatory capacity. Trial patients having undergone monocyte-interfering pharmacotherapy prior to monocyte harvest was associated with an impaired DC-based immunotherapy product outcome. Certain combinations of anti-cancer treatment resulted in a similar pattern of inadequate DC parameters, namely, a combination of temozolomide with irinotecan was associated with DCs showing poor maturation and decreased immunostimulatory features, and a combination of pazopanib, topotecan, and MTD-based cyclophosphamide was associated with poor monocyte differentiation and decreased DC immunostimulatory parameters. Searching for a surrogate marker predicting an adverse outcome of DC manufacture in the peripheral blood complete blood count prior to monocyte harvest, we observed an association between an increased number of immature granulocytes in peripheral blood and decreased potency of the DC-based product as quantified by allo-MLR. We conclude that the DC-manufacturing yield and the immunostimulatory quality of anti-cancer DC-based vaccines generated from the monocytes of patients were not influenced by the monocyte isolation modality but were detrimentally affected by the specific combination of anti-cancer agents used prior to monocyte harvest.
Návaznosti
LM2015090, projekt VaVNázev: Český národní uzel Evropské sítě infrastruktur klinického výzkumu (Akronym: CZECRIN)
Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Velké infrastruktury pro výzkum, vývoj a inovace
MUNI/A/1586/2018, interní kód MUNázev: Personalizovaná léčba v dětské onkologii: na cestě k "liquid dynamic medecine" a "N-of-1 clinical trials" (Akronym: Personalizovaná léčba v dětské onkologii)
Investor: Masarykova univerzita, Grantová agentura MU, DO R. 2020_Kategorie A - Specifický výzkum - Studentské výzkumné projekty
VytisknoutZobrazeno: 22. 9. 2020 19:31