Antitumor activity associated with prolonged persistence of adoptively transferred NY-ESO-1(c259)T cells in synovial sarcoma Journal Article
| Authors: | D’Angelo, S. P.; Melchiori, L.; Merchant, M. S.; Bernstein, D.; Glod, J.; Kaplan, R.; Grupp, S.; Tap, W. D.; Chagin, K.; Binder, G. K.; Basu, S.; Lowther, D. E.; Wang, R.; Bath, N.; Tipping, A.; Betts, G.; Ramachandran, I.; Navenot, J. M.; Zhang, H.; Wells, D. K.; Van Winkle, E.; Kari, G.; Trivedi, T.; Holdich, T.; Pandite, L.; Amado, R.; Mackall, C. L. |
| Article Title: | Antitumor activity associated with prolonged persistence of adoptively transferred NY-ESO-1(c259)T cells in synovial sarcoma |
| Abstract: | We evaluated the safety and activity of autologous T cells expressing NY-ESO-1c259, an affinity-enhanced T-cell receptor (TCR) recognizing an HLA-A2–restricted NY-ESO-1/LAGE1a–derived peptide, in patients with metastatic synovial sarcoma (NY-ESO-1c259T cells). Confirmed antitumor responses occurred in 50% of patients (6/12) and were characterized by tumor shrinkage over several months. Circulating NY-ESO-1c259T cells were present postinfusion in all patients and persisted for at least 6 months in all responders. Most of the infused NY-ESO-1c259T cells exhibited an effector memory phenotype following ex vivo expansion, but the persisting pools comprised largely central memory and stem-cell memory subsets, which remained polyfunctional and showed no evidence of T-cell exhaustion despite persistent tumor burdens. Next-generation sequencing of endogenous TCRs in CD8+ NY-ESO-1c259T cells revealed clonal diversity without contraction over time. These data suggest that regenerative pools of NY-ESO-1c259T cells produced a continuing supply of effector cells to mediate sustained, clinically meaningful antitumor effects. SIGNIFICANCE: Metastatic synovial sarcoma is incurable with standard therapy. We employed engineered T cells targeting NY-ESO-1, and the data suggest that robust, self-regenerating pools of CD8+ NY-ESO-1c259T cells produce a continuing supply of effector cells over several months that mediate clinically meaningful antitumor effects despite prolonged exposure to antigen. © 2018 American Association for Cancer Research. |
| Journal Title: | Cancer Discovery |
| Volume: | 8 |
| Issue: | 8 |
| ISSN: | 2159-8274 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2018-08-01 |
| Start Page: | 944 |
| End Page: | 957 |
| Language: | English |
| DOI: | 10.1158/2159-8290.cd-17-1417 |
| PROVIDER: | scopus |
| PUBMED: | 29891538 |
| PMCID: | PMC8092079 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 October 2018 -- Source: Scopus |
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