Format

Send to

Choose Destination
Nat Med. 2015 Aug;21(8):914-921. doi: 10.1038/nm.3910. Epub 2015 Jul 20.

NY-ESO-1-specific TCR-engineered T cells mediate sustained antigen-specific antitumor effects in myeloma.

Author information

1
The Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD, USA.
2
Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
3
Adaptimmune Ltd, Oxford, UK.
4
Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD USA.
5
Department of Pathology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
6
School of Mathematics and Statistics, Carleton University, Ottawa, Canada.
7
Cambridge Biomedical, Cambridge, Massachusetts, USA.
#
Contributed equally

Abstract

Despite recent therapeutic advances, multiple myeloma (MM) remains largely incurable. Here we report results of a phase I/II trial to evaluate the safety and activity of autologous T cells engineered to express an affinity-enhanced T cell receptor (TCR) recognizing a naturally processed peptide shared by the cancer-testis antigens NY-ESO-1 and LAGE-1. Twenty patients with antigen-positive MM received an average 2.4 × 10(9) engineered T cells 2 d after autologous stem cell transplant. Infusions were well tolerated without clinically apparent cytokine-release syndrome, despite high IL-6 levels. Engineered T cells expanded, persisted, trafficked to marrow and exhibited a cytotoxic phenotype. Persistence of engineered T cells in blood was inversely associated with NY-ESO-1 levels in the marrow. Disease progression was associated with loss of T cell persistence or antigen escape, in accordance with the expected mechanism of action of the transferred T cells. Encouraging clinical responses were observed in 16 of 20 patients (80%) with advanced disease, with a median progression-free survival of 19.1 months. NY-ESO-1-LAGE-1 TCR-engineered T cells were safe, trafficked to marrow and showed extended persistence that correlated with clinical activity against antigen-positive myeloma.

PMID:
26193344
PMCID:
PMC4529359
DOI:
10.1038/nm.3910
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center