Format

Send to

Choose Destination
J Immunol. 2014 Nov 1;193(9):4739-47. doi: 10.4049/jimmunol.1401550. Epub 2014 Sep 29.

A novel method using blinatumomab for efficient, clinical-grade expansion of polyclonal T cells for adoptive immunotherapy.

Author information

1
Centro di Terapia Cellulare, "G. Lanzani," USC Ematologia, Azienda Ospedaliera Papa Giovanni XXIII, 24127 Bergamo, Italy; jgolay@hpg23.it.
2
Centro di Terapia Cellulare, "G. Lanzani," USC Ematologia, Azienda Ospedaliera Papa Giovanni XXIII, 24127 Bergamo, Italy;
3
Centro Trapianto Midollo Osseo, USC Ematologia, Azienda Ospedaliera Papa Giovanni XXIII, 24127 Bergamo, Italy;
4
Nerviano Medical Sciences, 20014 Nerviano, Italy; and.
5
Global Clinical Development, Amgen, Thousand Oaks, CA 91320.

Abstract

Current treatment of chronic lymphocytic leukemia (CLL) patients often results in life-threatening immunosuppression. Furthermore, CLL is still an incurable disease due to the persistence of residual leukemic cells. These patients may therefore benefit from immunotherapy approaches aimed at immunoreconstitution and/or the elimination of residual disease following chemotherapy. For these purposes, we designed a simple GMP-compliant protocol for ex vivo expansion of normal T cells from CLL patients' peripheral blood for adoptive therapy, using bispecific Ab blinatumomab (CD3 × CD19), acting both as T cell stimulator and CLL depletion agent, and human rIL-2. Starting from only 10 ml CLL peripheral blood, a mean 515 × 10(6) CD3(+) T cells were expanded in 3 wk. The resulting blinatumomab-expanded T cells (BET) were polyclonal CD4(+) and CD8(+) and mostly effector and central memory cells. The Th1 subset was slightly prevalent over Th2, whereas Th17 and T regulatory cells were <1%. CMV-specific clones were detected in equivalent proportion before and after expansion. Interestingly, BET cells had normalized expression of the synapse inhibitors CD272 and CD279 compared with starting T cells and were cytotoxic against CD19(+) targets in presence of blinatumomab in vitro. In support of their functional capacity, we observed that BET, in combination with blinatumomab, had significant therapeutic activity in a systemic human diffuse large B lymphoma model in NOD-SCID mice. We propose BET as a therapeutic tool for immunoreconstitution of heavily immunosuppressed CLL patients and, in combination with bispecific Ab, as antitumor immunotherapy.

PMID:
25267972
DOI:
10.4049/jimmunol.1401550
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center