PSMA-Directed CAR T Cells Combined with Low-Dose Docetaxel Treatment Induce Tumor Regression in a Prostate Cancer Xenograft Model.
Mol Ther Oncolytics
; 18: 226-235, 2020 Sep 25.
Article
en En
| MEDLINE
| ID: mdl-32728611
ABSTRACT
While chimeric antigen receptor (CAR) T cell immunotherapy targeting CD19 has shown remarkable success in patients with lymphoid malignancies, the potency of CAR T cells in solid tumors is low so far. To improve the efficacy of CAR T cells targeting prostate carcinoma, we designed a novel CAR that recognizes a new epitope in the prostate-specific membrane antigen (PSMA) and established novel paradigms to apply CAR T cells in a preclinical prostate cancer model. In vitro characterization of the D7 single-chain antibody fragment-derived anti-PSMA CAR confirmed that the choice of the co-stimulatory domain is a major determinant of CAR T cell activation, differentiation, and exhaustion. In vivo, focal injections of the PSMA CAR T cells eradicated established human prostate cancer xenografts in a preclinical mouse model. Moreover, systemic intravenous CAR T cell application significantly inhibited tumor growth in combination with non-ablative low-dose docetaxel chemotherapy, while docetaxel or CAR T cell application alone was not effective. In conclusion, the focal application of D7-derived CAR T cells and their combination with chemotherapy represent promising immunotherapeutic avenues to treat local and advanced prostate cancer in the clinic.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Idioma:
En
Revista:
Mol Ther Oncolytics
Año:
2020
Tipo del documento:
Article
País de afiliación:
Alemania