Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

Blinatumomab induces autologous T cell killing of chronic lymphocytic leukemia cells

Wong, Ryan Francis, Pepper, Christopher John, Brennan, Paul, Nagorsen, Dirk, Man, Stephen Tzekwung and Fegan, Christopher Daniel 2013. Blinatumomab induces autologous T cell killing of chronic lymphocytic leukemia cells. Haematologica 98 (12) , pp. 1930-1938. 10.3324/haematol.2012.082248

Full text not available from this repository.

Abstract

Chronic lymphocytic leukemia is an incurable B-cell malignancy that is associated with tumor cell-mediated T-cell dysfunction. It therefore represents a challenging disease for T-cell immunotherapeutics. The CD19/CD3 bi-specific antibody construct blinatumomab (AMG103 or MT103) has been tested clinically in non-Hodgkin's lymphoma and acute lymphoblastic leukemia but has not been assessed in chronic lymphocytic leukemia. We tested whether blinatumomab could overcome T cell dysfunction in chronic lymphocytic leukemia in vitro. Blinatumomab was tested on PBMC from 28 patients (treatment naive and previously treated). T cell activation and function, as well as cytotoxicity against leukemic tumor cells were measured. Blinatumomab induced T-cell activation, proliferation, cytokine secretion and granzyme B release in a manner similar to stimulation with anti-CD3/anti-CD28 beads. However, only blinatumomab was able to induce tumor cell death and this was found to require blinatumomab-mediated conjugate formation between T-cells and tumor cells. Cytotoxicity of tumor cells was observed at very low T cell:tumor cell ratios. A 3-D model based on confocal microscopy, suggested that up to 11 tumor cells could cluster round each T cell. Importantly, blinatumomab induced cytotoxicity against tumor cells in samples from both treatment naïve and treated patients, and in the presence of co-culture pro-survival signals. The potent cytotoxic action of blinatumomab on tumor cells appears to involve conjugation of T cells with tumor cells at both the activation and effector stages. The efficacy of Blinatumomab in vitro, suggests that the bi-specific antibody approach may be a powerful immunotherapeutic strategy in chronic lymphocytic leukemia.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Uncontrolled Keywords: Lymphocytes; Chronic Lymphocytic Leukemia; Cell Therapy and Immunotherapy
Additional Information: Online publication date: 28 June 2013.
Publisher: Ferrata Storti Foundation
ISSN: 0390-6078
Last Modified: 04 Jun 2017 05:35
URI: http://orca.cf.ac.uk/id/eprint/52339

Citation Data

Cited 9 times in Google Scholar. View in Google Scholar

Cited 36 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item