Targeting tumor specific translocations in sarcomas in pediatric patients for immunotherapy

Crystal Mackall, Jay Berzofsky, Lee J. Helman

Research output: Contribution to journalArticlepeer-review

Abstract

In an effort to develop more effective therapies for various sarcomas in pediatric patients, the authors have focused on using recurrent tumor- specific translocations as potential novel tumor antigens. In general, these translocations generate fusion transcription factors. Because cytotoxic T cell lymphocyte receptors recognize peptide fragments bound to major histocompatibility complex Class 1 molecules, it is possible that unique peptides spanning the translocation breakpoint region may be processed, bound to major histocompatibility complex Class I molecules and displayed on the tumor cell surface where they could be susceptible to cytotoxic T cell lymphocyte killing. The authors have investigated the PAX-3-FKHR fusion product seen in alveolar rhabdomyosarcoma, and the EWS-FLI-1 fusion product seen in Ewing's sarcoma. Peptides spanning these fusion regions contain potential major histocompatibility complex Class I and Class II binding motifs suggesting they may serve as novel T cell antigens. Preliminary mouse experiments suggest that cytotoxic T cell lymphocytes specific for the PAX-3- FKHR fusion peptide can be generated and can recognize and kill tumor cells bearing the PAX-3-FKHR fusion protein. Clinical trials are ongoing to determine whether this approach will be useful.

Original languageEnglish (US)
Pages (from-to)25-31
Number of pages7
JournalClinical orthopaedics and related research
Issue number373
DOIs
StatePublished - 2000

ASJC Scopus subject areas

  • Surgery
  • Orthopedics and Sports Medicine

Fingerprint Dive into the research topics of 'Targeting tumor specific translocations in sarcomas in pediatric patients for immunotherapy'. Together they form a unique fingerprint.

Cite this