1. Mutated PPP1R3B is recognized by T cells used to treat a melanoma patient who experienced a durable complete tumor regression.
- Author
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Lu YC, Yao X, Li YF, El-Gamil M, Dudley ME, Yang JC, Almeida JR, Douek DC, Samuels Y, Rosenberg SA, and Robbins PF
- Subjects
- Base Sequence, Clinical Trials as Topic, Flow Cytometry, Gene Knockdown Techniques, Gene Library, Humans, Lymphocyte Activation immunology, Male, Melanoma genetics, Molecular Sequence Data, Mutation, Phosphoprotein Phosphatases genetics, Protein Phosphatase 1 genetics, Reverse Transcriptase Polymerase Chain Reaction, Immunodominant Epitopes immunology, Immunotherapy, Adoptive methods, Lymphocytes, Tumor-Infiltrating immunology, Melanoma immunology, Phosphoprotein Phosphatases immunology, Protein Phosphatase 1 immunology
- 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 therapy 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.
- Published
- 2013
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