Imaging CAR T cell therapy with PSMA-targeted positron emission tomography.
Sci Adv
; 5(7): eaaw5096, 2019 07.
Article
em En
| MEDLINE
| ID: mdl-31281894
ABSTRACT
Chimeric antigen receptor (CAR) T cell therapy for hematologic malignancies is fraught with several unknowns, including number of functional T cells that engage target tumor, durability and subsequent expansion and contraction of that engagement, and whether toxicity can be managed. Non-invasive, serial imaging of CAR T cell therapy using a reporter transgene can address those issues quantitatively. We have transduced anti-CD19 CAR T cells with the prostate-specific membrane antigen (PSMA) because it is a human protein with restricted normal tissue expression and has an expanding array of positron emission tomography (PET) and therapeutic radioligands. We demonstrate that CD19-tPSMA(N9del) CAR T cells can be tracked with [18F]DCFPyL PET in a Nalm6 model of acute lymphoblastic leukemia. Divergence between the number of CD19-tPSMA(N9del) CAR T cells in peripheral blood and bone marrow and those in tumor was evident. These findings underscore the need for non-invasive repeatable monitoring of CAR T cell disposition clinically.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Imunoterapia Adotiva
/
Glutamato Carboxipeptidase II
/
Tomografia por Emissão de Pósitrons
/
Leucemia-Linfoma Linfoblástico de Células Precursoras
/
Antígenos de Superfície
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Sci Adv
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Estados Unidos