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

AP Rapoport, EA Stadtmauer, GK Binder-Scholl… - Nature medicine, 2015 - nature.com
AP Rapoport, EA Stadtmauer, GK Binder-Scholl, O Goloubeva, DT Vogl, SF Lacey…
Nature medicine, 2015nature.com
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 …
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.
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