Development of a personalized dendritic cell vaccine and single-cell RNA sequencing-guided assessment of its cell type composition.
Cytotherapy
; 25(2): 210-219, 2023 02.
Article
em En
| MEDLINE
| ID: mdl-36443171
ABSTRACT
BACKGROUND AIMS:
Dendritic cell (DC)-based immunotherapy is a promising approach to treat cancer; however, there is no consensus on the manufacturing processes. Cell type heterogeneity in products manufactured by various methods is understudied and may elicit safety concerns from the regulatory perspective.METHODS:
We characterized the cell type composition of a recently developed DC vaccine, CUD-002, consisting of DCs loaded with mRNA encoding personalized tumor neoantigens (NCT05270720).RESULTS:
Using single-cell transcriptomic analysis as an unbiased approach, we found that >80% cells in the final product were DCs and the rest primarily comprised myelocytes and lymphocytes. Subsequent fluorescence-activated cell sorting analyses confirmed these cellular identities. These results indicate that unintended cells originate from leukapheresis, the first step of the manufacturing process, and thus likely safe. Consistently, no overt toxicity or tumorigenicity was observed in mice inoculated with CUD-002.CONCLUSIONS:
Considering that leukapheresis is a widely used procedure for collecting diverse peripheral blood cell types to manufacture various cytotherapies, this study establishes a workflow to analyze and address regulatory considerations on cell type heterogeneity.Palavras-chave
Texto completo:
1
Eixos temáticos:
Pesquisa_clinica
Base de dados:
MEDLINE
Assunto principal:
Vacinas
/
Vacinas Anticâncer
/
Neoplasias
Limite:
Animals
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article