Integrating Proteomics and Transcriptomics for Systematic Combinatorial Chimeric Antigen Receptor Therapy of AML.
Cancer Cell
; 32(4): 506-519.e5, 2017 10 09.
Article
en En
| MEDLINE
| ID: mdl-29017060
Chimeric antigen receptor (CAR) therapy targeting CD19 has yielded remarkable outcomes in patients with acute lymphoblastic leukemia. To identify potential CAR targets in acute myeloid leukemia (AML), we probed the AML surfaceome for overexpressed molecules with tolerable systemic expression. We integrated large transcriptomics and proteomics datasets from malignant and normal tissues, and developed an algorithm to identify potential targets expressed in leukemia stem cells, but not in normal CD34+CD38- hematopoietic cells, T cells, or vital tissues. As these investigations did not uncover candidate targets with a profile as favorable as CD19, we developed a generalizable combinatorial targeting strategy fulfilling stringent efficacy and safety criteria. Our findings indicate that several target pairings hold great promise for CAR therapy of AML.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Receptores de Antígenos de Linfocitos T
/
Linfocitos T
/
Leucemia Mieloide Aguda
/
Antígenos CD19
/
Perfilación de la Expresión Génica
/
Proteómica
/
Inmunoterapia
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Cancer Cell
Asunto de la revista:
NEOPLASIAS
Año:
2017
Tipo del documento:
Article
País de afiliación:
Estados Unidos