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: 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
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 190 Issue 12 Pg. 6034-42 (Jun 15 2013) ISSN: 1550-6606 [Electronic] United States
• PMID: 23690473 (Publication Type: Case Reports, Journal Article, Research Support, N.I.H., Intramural)

Chemical References

• Immunodominant Epitopes
• PPP1R3A protein, human
• PPP1R3B protein, human
• Phosphoprotein Phosphatases
• Protein Phosphatase 1

Topics

• Base Sequence
• Clinical Trials as Topic
• Flow Cytometry
• Gene Knockdown Techniques
• Gene Library
• Humans
• Immunodominant Epitopes (immunology)
• Immunotherapy, Adoptive (methods)
• Lymphocyte Activation (immunology)
• Lymphocytes, Tumor-Infiltrating (immunology)
• Male
• Melanoma (genetics, immunology)
• Molecular Sequence Data
• Mutation
• Phosphoprotein Phosphatases (genetics, immunology)
• Protein Phosphatase 1 (genetics, immunology)
• Reverse Transcriptase Polymerase Chain Reaction