A superagonist variant of peptide MART1/melan A27-35 elicits anti- melanoma CD8+ T cells with enhanced functional characteristics: Implication for more effective immunotherapy

Licia Rivoltini, Paola Squarcina, Douglas J. Loftus, Chiara Castelli, Paolo Tarsini, Arabella Mazzocchi, Francesca Rini, Vincenzo Viggiano, Filiberto Belli, Giorgio Parmiani

Research output: Contribution to journalArticlepeer-review

Abstract

In the present study, we show that a singly substituted peptide derived from the epitope MART127-35 and containing a Leu in position 1 (LAGIGILTV; 1L) behaves as a superagonist by in vitro inducing specific T cells with enhanced immunological functions. 1L-specific CTLs can be raised from peripheral blood of HLA-A2+ melanoma patients more efficiently than T cells specific for the cognate peptide. These T cells show a greater sensitivity to native MART127-35 when compared with CTL variable raised to parental peptide from the same patients. More importantly, anti-1L but not anti-native T cells display high levels of interferon γ production at early time points, and readily secreted interleukin-2 in response to native epitope endogenously presented by melanoma cells. Additionally, anti-1L T cells are insensitive to the inhibitory effects of MART127-35 natural analogues that antagonize the lytic response of CTLs raised to the cognate peptide. Analysis of T-cell receptor variable β usage suggests that the native and 1L peptides stimulate different components of the MART127-35-reactive T cell population. These data provide rationale to the use of superagonist analogues of tumor antigens for inducing in vivo immunization potentially able to overcome tumor immune escape and mediate a more significant control of tumor growth.

Original languageEnglish
Pages (from-to)301-306
Number of pages6
JournalCancer Research
Volume59
Issue number2
Publication statusPublished - Jan 16 1999

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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