The Waardenburg syndrome type 4 gene, SOX10, is a novel tumor-associated antigen identified in a patient with a dramatic response to immunotherapy

Cancer Res. 2002 Jun 1;62(11):3020-3.

Abstract

In this study, we have identified, for the first time, the presence of de novo cellular immune reactivity against the transcription factor SOX10, using tumor-infiltrating lymphocytes obtained from a patient who experienced a dramatic clinical response to immunotherapy. SOX10 acts as a critical transactivator of tyrosinase-related protein-2 during melanoblast development and a potent transactivator of micropthalmia-associated transcription factor, which is considered to be a master gene that controls the development and postnatal survival of melanocytes. Mutations in SOX10 result in Waardenburg syndrome type 4. The overlapping epitopes AWISKPPGV and SAWISKPPGV, designated SOX10: 332-340 and SOX10: 331-340, respectively, were recognized by tumor-infiltrating lymphocyte clone M37 in an HLA-A2-restricted fashion.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antigens, Neoplasm / biosynthesis
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / immunology*
  • Clone Cells
  • DNA, Complementary / genetics
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / immunology*
  • Epitopes, T-Lymphocyte / immunology
  • Female
  • High Mobility Group Proteins / biosynthesis
  • High Mobility Group Proteins / genetics
  • High Mobility Group Proteins / immunology*
  • Humans
  • Immunotherapy, Active
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Melanoma / genetics
  • Melanoma / immunology*
  • Melanoma / therapy
  • Middle Aged
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • SOXE Transcription Factors
  • Transcription Factors
  • Waardenburg Syndrome / genetics

Substances

  • Antigens, Neoplasm
  • DNA, Complementary
  • DNA-Binding Proteins
  • Epitopes, T-Lymphocyte
  • High Mobility Group Proteins
  • RNA, Messenger
  • SOX10 protein, human
  • SOXE Transcription Factors
  • Transcription Factors