| RRC ID |
88489
|
| Author |
Nakamura M, Meguri Y, Ikegawa S, Kondo T, Sumii Y, Fukumi T, Iwamoto M, Sando Y, Sugiura H, Asada N, Ennishi D, Tomida S, Fukuda-Kawaguchi E, Ishii Y, Maeda Y, Matsuoka KI.
|
| Title |
Reduced dose of PTCy followed by adjuvant α-galactosylceramide enhances GVL effect without sacrificing GVHD suppression.
|
| Journal |
Sci Rep
|
| Abstract |
Posttransplantation cyclophosphamide (PTCy) has become a popular option for haploidentical hematopoietic stem cell transplantation (HSCT). However, personalized methods to adjust immune intensity after PTCy for each patient's condition have not been well studied. Here, we investigated the effects of reducing the dose of PTCy followed by α-galactosylceramide (α-GC), a ligand of iNKT cells, on the reciprocal balance between graft-versus-host disease (GVHD) and the graft-versus-leukemia (GVL) effect. In a murine haploidentical HSCT model, insufficient GVHD prevention after reduced-dose PTCy was efficiently compensated for by multiple administrations of α-GC. The ligand treatment maintained the enhanced GVL effect after reduced-dose PTCy. Phenotypic analyses revealed that donor-derived B cells presented the ligand and induced preferential skewing to the NKT2 phenotype rather than the NKT1 phenotype, which was followed by the early recovery of all T cell subsets, especially CD4+Foxp3+ regulatory T cells. These studies indicate that α-GC administration soon after reduced-dose PTCy restores GVHD-preventing activity and maintains the GVL effect, which is enhanced by reducing the dose of PTCy. Our results provide important information for the development of a novel strategy to optimize PTCy-based transplantation, particularly in patients with a potential relapse risk.
|
| Volume |
11(1)
|
| Pages |
13125
|
| Published |
2021-6-23
|
| DOI |
10.1038/s41598-021-92526-z
|
| PII |
10.1038/s41598-021-92526-z
|
| PMID |
34162921
|
| PMC |
PMC8222309
|
| MeSH |
Adjuvants, Pharmaceutic / therapeutic use
Animals
B-Lymphocytes / drug effects
Bone Marrow Transplantation / adverse effects
Cyclophosphamide / therapeutic use*
Dendritic Cells / drug effects
Dose-Response Relationship, Drug
Female
Galactosylceramides / therapeutic use*
Graft vs Host Disease / prevention & control*
Graft vs Leukemia Effect / drug effects*
Macrophages / drug effects
Mice
Mice, Inbred C57BL
|
| IF |
3.998
|
| Resource |
| Mice |
RBRC00144 |
