in vivo and in vitro Anti-Tumor Efficiency by Tumor-Specific CD8+ CTL Induced with Tumor Associated Peptide / 中国肿瘤生物治疗杂志

ABSTRACT

The aim of the current study was to determine whether tumor-specific T cells can be primed in and obtained from sponge implants loaded with tumor associated peptides. Naive C57BL/6 mice as well as C57BL/6 mice previously primed with FBL-3 tumor cells were implanted with small polyurethane sponges containing FBL-3 gag peptides CCLCLTVFL(gPr80 gag 85-93)or RSPTNLAKV(Pr65 gag p30 131-139). Both FBL-3 gag peptides were shown could bind to H-2 Db molecules. Ten days later, cells that had accumulated in the sponges were harvested, stimulated in vitro with the immunizing peptide, and tested for cytolytic activity against FBL-3 tumor and FBL-3 gag peptides. The results demonstrated that peptide-specific CD8+ CTL could be elicited and obtained from the sponge implants of both naive and immune mice. The FBL-3 gag p85-93 peptide induced CTL could specifically lyse syngeneic targets pulsed with the FBL-3 gag p85-93 peptide as well as FBL-3 tumor. However, the FBL-3 gag p131-139 peptide induced CTL lysed only the FBL-3 gag p131- 139 peptide pulsed syngeneic targets but not the FBL- 3 tumor. Tumor-specific T cells obtained from peptide-loaded sponge implants could be induced to grow to large numbers in vitro by periodic restimulation with the immunizing peptide plus syngeneic APC and low concentrations of IL- 2. Adoptive transfer of the resultant expanded FBL-3 gag p85-93 peptide-induced CTL into mice with disseminated FBL-3 could mediate effective anti-tumor therapy. Thus,in vivo immunization with peptide-loaded sponges provides a potentially useful technique for procuring primed peptide- specific T cells for tumor therapy.