Details

Autor(en) / Beteiligte

• Rapoport, Aaron P
• Stadtmauer, Edward A
• Binder-Scholl, Gwendolyn K
• Goloubeva, Olga
• Vogl, Dan T
• Lacey, Simon F
• Badros, Ashraf Z
• Garfall, Alfred
• Weiss, Brendan
• Finklestein, Jeffrey
• Kulikovskaya, Irina
• Sinha, Sanjoy K
• Kronsberg, Shari
• Gupta, Minnal
• Bond, Sarah
• Melchiori, Luca
• Brewer, Joanna E
• Bennett, Alan D
• Gerry, Andrew B
• Pumphrey, Nicholas J
• Williams, Daniel
• Tayton-Martin, Helen K
• Ribeiro, Lilliam
• Holdich, Tom
• Yanovich, Saul
• Hardy, Nancy
• Yared, Jean
• Kerr, Naseem
• Philip, Sunita
• Westphal, Sandra
• Siegel, Don L
• Levine, Bruce L
• Jakobsen, Bent K
• Kalos, Michael
• June, Carl H

Titel

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

Ist Teil von

• Nature medicine, 2015-08, Vol.21 (8), p.914-921

Ort / Verlag

United States: Nature Publishing Group

Erscheinungsjahr

2015

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.