Cancer Immunology, Immunotherapy

, Volume 55, Issue 9, pp 1142–1150

T-cell receptor tetramer binding or the lack there of does not necessitate antigen reactivity in T-cell receptor transduced T cells

  • Gretchen E. Lyons
  • Jeffrey J. Roszkowski
  • Stephen Man
  • Cassian Yee
  • W. Martin Kast
  • Michael I. Nishimura
Original Article

DOI: 10.1007/s00262-005-0103-9

Cite this article as:
Lyons, G.E., Roszkowski, J.J., Man, S. et al. Cancer Immunol Immunother (2006) 55: 1142. doi:10.1007/s00262-005-0103-9

Abstract

Genetic transfer of T-cell receptor (TCR) chains provides a means of transferring tumor antigen specificity onto an alternate T-cell population. To determine which tumor reactive TCRs are best suitable for such adoptive transfer, careful evaluation of the resulting TCR modified populations need to be performed. We have previously cloned, and expressed TCRs from melanoma, EBV, HCV, and HPV reactive T-cell clones and found that several routine indicators of T-cell function do not always predict the relative strength of a TCR. Using a combination of tetramer binding assays and antigen recognition assays, we identified TCRs that fall into three classes. One class of TCR did not bind tetramers yet resulted in cells with high avidity for antigen. A second TCR class bound tetramer but did not secrete cytokines in response to antigen. Finally, the third class of TCRs bound tetramer and reacted to antigen as would be expected. We conclude that tetramer binding is not always a good indicator of the function of a cloned TCR or the avidity of a TCR gene modified T cell. Furthermore, our data indicate that the use of tetramer binding alone to identify antigen reactive TCRs may result in the exclusion of TCRs that may be highly reactive or cross reactive to the relevant tumor antigen.

Keywords

T-cell receptor Transduction Immunotherapy Tetramer 

Abbreviations

TCR

T-cell receptor

TIL

Tumor-infiltrating lymphocytes

TAA

Tumor-associated antigen

AV/BV, TCR

α/β chain variable regions

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Gretchen E. Lyons
    • 1
  • Jeffrey J. Roszkowski
    • 1
  • Stephen Man
    • 2
  • Cassian Yee
    • 3
  • W. Martin Kast
    • 4
  • Michael I. Nishimura
    • 1
  1. 1.Department of Surgery and Committee of ImmunologyThe University of ChicagoChicagoUSA
  2. 2.Department of Medical Biochemistry and Immunology, School of MedicineCardiff UniversityCardiffUK
  3. 3.Fred Hutchinson Cancer Research CenterSeattleUSA
  4. 4.Department of Molecular Microbiology and Immunology, Norris Comprehensive Cancer CenterUniversity of Southern CaliforniaLos AngelesUSA

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