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

By A. Rapoport, E. Stadtmauer, G. Binder-Scholl, O. Goloubeva, D. Vogl, S. Lacey, A. Badros, A. Garfall, B. Weiss, J. Finklestein and 25 more. Nature Medicine, 2015

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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 × 109 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.

Subfields: Immunology, Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/15d02588caf87a6d09b2805a9b09c012f765a413

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Citations in the corpus

CRISPR-engineered T cells in patients with refractory cancer (2020, methodology): “Recent studies have shown safety and promising efficacy of such adoptive T cell transfer approaches using transgenic TCRs specific for the immunogenic NY-ESO-1 tumor antigen in patients withmyeloma,melanoma, and sarcoma (10–12).”
Membrane-Proximal Epitope Facilitates Efficient T Cell Synapse Formation by Anti-FcRH5/CD3 and Is a Requirement for Myeloma Cell Killing (2017, background): “Published by Elsevier Inc. 383 er the CC BY license (http://creativecommons.org/licenses/by/4.0/). and have demonstrated promising activity in myeloma (Garfall et al., 2015; Rapoport et al., 2015).”
The Principles of Engineering Immune Cells to Treat Cancer (2017, background): “Objective clinical responses were observed in synovial cell sarcoma, melanoma, and myeloma in the first two trials (Rapoport et al., 2015; Robbins et al., 2011).”