RRC ID 73377
著者 Nakajima K, Shen Z, Miura M, Nakabayashi H, Kawahara M.
タイトル Sequential control of myeloid cell proliferation and differentiation by cytokine receptor-based chimeric antigen receptors.
ジャーナル PLoS One
Abstract As chimeric antigen receptor (CAR)-T cell therapy has been recently applied in clinics, controlling the fate of blood cells is increasingly important for curing blood disorders. In this study, we aim to construct proliferation-inducing and differentiation-inducing CARs (piCAR and diCAR) with two different antigen specificities and express them simultaneously on the cell surface. Since the two antigens are non-cross-reactive and exclusively activate piCAR or diCAR, sequential induction from cell proliferation to differentiation could be controlled by switching the antigens added in the culture medium. To demonstrate this notion, a murine myeloid progenitor cell line 32Dcl3, which proliferates in an IL-3-dependent manner and differentiates into granulocytes when cultured in the presence of G-CSF, is chosen as a model. To mimic the cell fate control of 32Dcl3 cells, IL-3R-based piCAR and G-CSFR-based diCAR are rationally designed and co-expressed in 32Dcl3 cells to evaluate the proliferation- and differentiation-inducing functions. Consequently, the sequential induction from proliferation to differentiation with switching the cytokine from IL-3 to G-CSF is successfully replaced by switching the antigen from one to another in the CARs-co-expressing cells. Thus, piCAR and diCAR may become a platform technology for sequentially controlling proliferation and differentiation of various cell types that need to be produced in cell and gene therapies.
巻・号 17(12)
ページ e0279409
公開日 2022-1-1
DOI 10.1371/journal.pone.0279409
PII PONE-D-22-21208
PMID 36574389
PMC PMC9794043
MeSH Animals Cell Differentiation Cell Proliferation Granulocyte Colony-Stimulating Factor / pharmacology Interleukin-3 / metabolism Mice Myeloid Progenitor Cells / metabolism Receptors, Chimeric Antigen* / genetics Receptors, Cytokine
IF 2.74
リソース情報
ヒト・動物細胞 32Dcl3(RCB1377)