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CD8 T-cell recognition of human 5T4 oncofetal antigen

Lucy J C Smyth1, Eyad Elkord, Taher E I Taher

  • 1Immunology Group, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, United Kingdom.

International Journal of Cancer
|April 29, 2006
PubMed

Insights

Researchers generated human CD8 T cells targeting the 5T4 oncofetal antigen for cancer immunotherapy. They identified specific HLA-A*0201 epitopes that recognize 5T4-positive tumor cells, offering a promising avenue for therapeutic development.

Area of Science:

  • Immunology
  • Oncology
  • Vaccinology

Background:

  • The 5T4 oncofetal antigen is prevalent in various human carcinomas, indicating its potential as a target for cancer immunotherapy.
  • Previous preclinical studies showed success with an MVA vaccine encoding the 5T4 antigen in a murine model.

Purpose of the Study:

  • To generate human CD8 T cells specific for the 5T4 antigen.
  • To identify potential HLA-A*0201-presented epitopes of the 5T4 antigen for targeted immunotherapy.

Main Methods:

  • Human CD8 T cells were generated by stimulating autologous monocyte-derived dendritic cells (DCs) with a replication-defective adenovirus encoding the 5T4 cDNA (Ad5T4).
  • Epitopes were identified using proteasome digestion of peptides and computational prediction algorithms.
  • T cell responses were assessed via cytotoxicity assays, IFN-gamma ELISPOT, and ELISA, with recognition of tumor cells evaluated based on HLA-A*0201 expression.

Main Results:

  • A repertoire of CD8 T cell responses specific to the 5T4 antigen was confirmed across multiple donors.
  • Eight putative HLA-A*0201-presented CD8 MHC class I epitopes of the 5T4 antigen were identified.
  • Two epitopes successfully generated specific CD8 T cells that recognized naturally 5T4-positive tumor cells expressing HLA-A*0201.

Conclusions:

  • There is a natural repertoire of CD8 T cell recognition of the 5T4 antigen in healthy individuals.
  • Candidate HLA-A*0201 epitopes of 5T4 have been identified, paving the way for the development of targeted immunotherapies against 5T4-expressing carcinomas.

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