Induction of antitumor immunity by proteasome-inhibited syngeneic fibroblasts pulsed with a modified TAA peptide

Khaled M. El-Shami, Boaz Tirosh, Dan Popovic, Lior Carmon, Esther Tzehoval, Ezra Vadai, Michael Feldman, Lea Eisenbach*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

CTLs specific for tumor antigens play a major role in immunity against cancer. Improved binding affinity of putative TAA peptides could enhance the in vivo immunogenicity of these self-altered self- tumor antigens. We examined here the efficacy of tumor vaccines composed of an altered peptide ligand of MUT-I, designated MUT-D, which exhibited significantly higher class-I allele Kb binding affinity than its native counterpart MUT-I. The peptide was loaded on antigen presenting cells composed of the C57BL/6- syngeneic fibroblast cell line BLK.CL4. These cells were treated with proteasome inhibitor in order to shut off the degradation of proteins and the subsequent loading of endogenous peptides onto MHC class-I molecules, thus allowing for the pulsing of these cells with the modified peptide MUT-D. Proteasome-inhibited and modified peptide-loaded fibroblasts induced a peptide-specific CTL that significantly delayed primary tumor progression and protected the pre-immunized mice against the development of lung metastasis following the surgical removal of the primary tumor. Genetic modification of the fibroblasts to express the immunostimulatory cytokine IL-2 did not improve the APC function of the modified cells, nor did it result in augmentation of the potency of the vaccine. Our results suggest that the proteasome-inhibited fibroblasts pulsed with modified, high binder tumor- associated antigen peptide are good antigen-presenting cells and represent an effective form of tumor vaccine.

Original languageAmerican English
Pages (from-to)236-242
Number of pages7
JournalInternational Journal of Cancer
Volume85
Issue number2
DOIs
StatePublished - 15 Jan 2000
Externally publishedYes

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