Loop CD20/CD19 CAR-T cells eradicate B-cell malignancies efficiently.
Sci China Life Sci
; 66(4): 754-770, 2023 04.
Article
de En
| MEDLINE
| ID: mdl-36251156
ABSTRACT
CD19 chimeric antigen receptor (CAR) T cells have shown robust efficacy in relapsed and refractory acute lymphoblastic leukemia (R/R ALL), but compromising result in chronic lymphoblastic leukemia (CLL) and non-Hodgkin's lymphoma (NHL). CD19 relapse and the lack of CAR-T cell persistence which result in treatment failure are considerable obstacles to overcome. CAR-T targeting CD20 is an option for salvaging CD19 CAR-T failure. Previous studies have established variant structures of bispecific CAR-T which could avoid antigen-loss and immune escape. Here, we constructed tandem and loop CAR structures targeting both CD19 and CD20 antigen. Bispecific CAR-T cells could eliminate either CD19 or CD20 negative lymphoma cells, suggesting they exhibited dual antigen targeting of CD19 and CD20. By comparing the efficiency of four bispecific CAR modified T cells, it was found that loop2019 CAR was the best structure among them to eradicate lymphoma cell lines and patients' primary lymphoma or CLL cells in a very low dose in vitro and prolong the survival time dramatically in lymphoma xenograft mice model. These data highlighted the potential of loop2019 CAR-T in clinical treatment.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Leucémie chronique lymphocytaire à cellules B
/
Récepteurs chimériques pour l'antigène
/
Lymphomes
Limites:
Animals
/
Humans
Langue:
En
Journal:
Sci China Life Sci
Sujet du journal:
BIOLOGIA
/
CIENCIA
Année:
2023
Type de document:
Article
Pays d'affiliation:
Chine