T lymphocytes can be effectively recruited for ex vivo and in vivo lysis of AML blasts by a novel CD33/CD3-bispecific BiTE antibody construct.
Leukemia
; 27(5): 1107-15, 2013 Apr.
Article
de En
| MEDLINE
| ID: mdl-23178753
ABSTRACT
Patients with acute myelogenous leukemia (AML) are in high need of novel targeted therapies. Here we explored the ex vivo activity of AMG330, a novel T-cell-engaging BiTE (bi-specific T-cell engagers) antibody (Ab) construct, that is bispecific for the myeloid differentiation antigen, CD33 and CD3, in primary samples from AML patients (N=23) and AML cell lines. KG-1 and U937 cells were lysed in co-culture with healthy donor T-cells at AMG330 concentrations as low as 0.1 ng/ml (1.8 pM). T-cells derived from AML patient samples were found to be as active in redirected lysis by AMG330 as T-cells from healthy donors. In an autologous setting, AMG330 could activate and expand T-cells in primary AML patient samples, and effectively mediated the redirected lysis of AML blasts and normal myeloid cells. A deficiency in target-cell lysis was only observed in samples with very low initial effector-to-target (ET) ratio. However, this could be overcome if previously stimulated autologous T-cells were tested in patient samples at a higher ET ratio. In vivo experiments in immunodeficient mice demonstrated significant inhibition of tumor growth by AMG330 and an inducible infiltration of human T-cells into subcutaneous HL60 tumors. The activities of the CD33/CD3-bispecific BiTE Ab construct AMG330 warrant further development for the treatment of AML.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Lymphocytes T
/
Leucémie aigüe myéloïde
/
Crise blastique
/
Antigènes CD3
/
Anticorps bispécifiques
/
Cytotoxicité immunologique
/
Lectine-3 de type Ig liant l'acide sialique
Limites:
Animals
/
Humans
Langue:
En
Journal:
Leukemia
Sujet du journal:
HEMATOLOGIA
/
NEOPLASIAS
Année:
2013
Type de document:
Article
Pays d'affiliation:
Allemagne