Mutated PPP1R3B is recognized by T cells used to treat a melanoma patient who experienced a durable complete tumor regression

Yong Chen Lu, Xin Yao, Yong F. Li, Mona El-Gamil, Mark E. Dudley, James C. Yang, Jorge R. Almeida, Daniel C. Douek, Yardena Samuels, Steven A. Rosenberg, Paul F. Robbins

Research output: Contribution to journalArticlepeer-review

Abstract

Adoptive cell therapy with tumor-infiltrating lymphocytes (TILs) represents an effective treatment for patients with metastatic melanoma. However, most of the Ag targets recognized by effective melanoma-reactive TILs remain elusive. In this study, patient 2369 experienced a complete response, including regressions of bulky liver tumor masses, ongoing beyond 7 y following adoptive TIL transfer. The screening of a cDNA library generated from the autologous melanoma cell line resulted in the isolation of a mutated protein phosphatase 1, regulatory (inhibitor) subunit 3B (PPP1R3B) gene product. The mutated PPP1R3B peptide represents the immunodominant epitope recognized by tumor-reactive T cells in TIL 2369. Five years following adoptive transfer, peripheral blood T lymphocytes obtained from patient 2369 recognized the mutated PPP1R3B epitope. These results demonstrate that adoptive T cell herapy targeting a tumor-specific Ag can mediate long-term survival for a patient with metastatic melanoma. This study also provides an impetus to develop personalized immunotherapy targeting tumor-specific, mutated Ags.

Original languageEnglish (US)
Pages (from-to)6034-6042
Number of pages9
JournalJournal of Immunology
Volume190
Issue number12
DOIs
StatePublished - Jun 15 2013

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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