title: Mutated PPP1R3B is recognized by T cells used to treat a melanoma patient who experienced a durable complete tumor regression.
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.
authors.affiliation: Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Yong-Chen
authors.initials: YC
authors.lastname: Lu
authors.forename: Xin
authors.initials: X
authors.lastname: Yao
authors.forename: Yong F
authors.initials: YF
authors.lastname: Li
authors.forename: Mona
authors.initials: M
authors.lastname: El-Gamil
authors.forename: Mark E
authors.initials: ME
authors.lastname: Dudley
authors.forename: James C
authors.initials: JC
authors.lastname: Yang
authors.forename: Jorge R
authors.initials: JR
authors.lastname: Almeida
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Douek
authors.forename: Yardena
authors.initials: Y
authors.lastname: Samuels
authors.forename: Steven A
authors.initials: SA
authors.lastname: Rosenberg
authors.forename: Paul F
authors.initials: PF
authors.lastname: Robbins
mesh_terms: D001483:Base Sequence; D002986:Clinical Trials as Topic; D005434:Flow Cytometry; D055785:Gene Knockdown Techniques; D015723:Gene Library; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology*; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008213:Lymphocyte Activation / Q000276:immunology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D008545:Melanoma / Q000235:genetics / Q000276:immunology*; D008969:Molecular Sequence Data; D009154:Mutation; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000276:immunology*; D054645:Protein Phosphatase 1 / Q000235:genetics / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D016056:Immunodominant Epitopes; C114205:PPP1R3A protein, human; C586823:PPP1R3B protein, human; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1