Therapeutic effectiveness of recombinant cancer vaccines is associated with a prevalent T-cell receptor α usage by melanoma-specific CD8+ T lymphocytes

Raffaele De Palma, Ilaria Marigo, Francesco Del Galdo, Carmela De Santo, Paolo Serafini, Sara Cingarlini, Thomas Tüting, Julia Lenz, Giuseppe Basso, Gabriella Milan, Paola Zanovello, Vincenzo Bronte

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Definition of immune variables that correlate with the antitumor activity of cancer vaccines is critical for monitoring immunotherapy protocols. To define surrogate end points predictive of the therapeutic efficacy of recombinant vaccines based on melanoma antigen tyrosinase-related protein (TRP)-2, we evaluated several properties of antigen-specific CD8+ T lymphocytes in single mice undergoing either prophylactic or therapeutic immunization. Predictive markers for the efficacy of genetic vaccination were identified in the prophylactic model used. Interestingly, the number of tetramer+ CD8+ T lymphocytes expanded in vitro after a single cycle of stimulation with the immunodominant TRP-2 peptide was of the highest predictive value. In the therapeutic model, no variable examined at a single mouse level predicted the long-term therapeutic effect. Mice that survived did not show the highest expansion of antigen-specific lymphocytes or the more functionally active effectors, ex vivo or after in vitro culture with the peptide antigen. Successful therapy correlated strictly with the skewing of the T-cell receptor repertoire of tetramer-sorted, TRP-2-specific CD8+ T lymphocytes, which showed a preferential α chain usage with a common CDR3 region.

Original languageEnglish (US)
Pages (from-to)8068-8076
Number of pages9
JournalCancer Research
Volume64
Issue number21
DOIs
StatePublished - Nov 1 2004
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    De Palma, R., Marigo, I., Del Galdo, F., De Santo, C., Serafini, P., Cingarlini, S., Tüting, T., Lenz, J., Basso, G., Milan, G., Zanovello, P., & Bronte, V. (2004). Therapeutic effectiveness of recombinant cancer vaccines is associated with a prevalent T-cell receptor α usage by melanoma-specific CD8+ T lymphocytes. Cancer Research, 64(21), 8068-8076. https://doi.org/10.1158/0008-5472.CAN-04-0067