An antigen-targeted approach to adoptive transfer therapy of cancer.

Valmori, D; Pittet, M; Rimoldi, D; Liénard, D; Dunbar, R; Cerundolo, V; Lejeune, F; Cerottini, J; Romero, P

Journal article

An antigen-targeted approach to adoptive transfer therapy of cancer.

Abstract:: Previous attempts to treat human malignancies by adoptive transfer of tumor-specific CTLs have been limited by the difficulty of isolating T cells of defined antigen specificity. The recent development of MHC class I/antigenic peptide tetrameric complexes that allow direct identification of antigen-specific T cells has opened new possibilities for the isolation and in vitro expansion of tumor-specific T cells. In the present study, we have derived polyclonal monospecific cell lines from circulating Melan-A-specific CTL precursors of HLA-A*0201+ melanoma patients by combining stimulation with recently identified peptide analogues of the immunodominant epitope from the melanoma-associated antigen Melan-A with staining with fluorescent HLA-A*0201/Melan-A peptide tetramers. In vitro expansion of antigen-specific CD8+ T cells was monitored by flow cytometry with the fluorescent tetramers and anti-CD8 monoclonal antibody. This analysis revealed that Melan-A 26-35 peptide analogues were much more efficient than the parental peptides in stimulating a rapid in vitro expansion of antigen-specific CD8+ T cells. These cells were then isolated by tetramer-guided cell sorting and subsequently expanded in vitro by mitogen stimulation. The resulting polyclonal but monospecific CTLs fully cross-recognized the parental peptides and were able to efficiently lyse Melan-A-expressing tumor cells. Altogether, these results pave the way to a molecularly defined approach to antigen-specific adoptive transfer therapy of cancer.

Publication status:: Published

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APA Style

Valmori, D., Pittet, M., Rimoldi, D., Liénard, D., Dunbar, R., Cerundolo, V., Lejeune, F., Cerottini, J., & Romero, P. (1999). An antigen-targeted approach to adoptive transfer therapy of cancer. Cancer Research, 59(9), 2167–2173.

MLA Style

Valmori, D., et al. “An Antigen-Targeted Approach to Adoptive Transfer Therapy of Cancer.” Cancer Research, vol. 59, no. 9, 1999, pp. 2167–73.

Chicago Style

Valmori, D, M Pittet, D Rimoldi, D Liénard, R Dunbar, V Cerundolo, F Lejeune, J Cerottini, and P Romero. 1999. “An Antigen-Targeted Approach to Adoptive Transfer Therapy of Cancer.” Cancer Research 59 (9): 2167–73.
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