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Clin Cancer Res. 2012 Sep 1;18(17):4850-60. doi: 10.1158/1078-0432.CCR-11-2776. Epub 2012 Jul 2.

Myeloma-specific multiple peptides able to generate cytotoxic T lymphocytes: a potential therapeutic application in multiple myeloma and other plasma cell disorders.

Author information

1
Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02115, USA.

Abstract

PURPOSE:

The efficacy of peptide vaccines may be enhanced by stimulating immune cells with multiple peptides derived from distinct tumor-associated antigens. We have evaluated the heteroclitic XBP1-US(184-192) (YISPWILAV), heteroclitic XBP1-SP(367-375) (YLFPQLISV), native CD138(260-268) (GLVGLIFAV), and native CS1(239-247) (SLFVLGLFL) peptides, which have strong HLA-A2 affinity and immunogenicity in combination, for their ability to elicit multiple myeloma antigen-specific responses.

EXPERIMENTAL DESIGN:

Multipeptide-specific cytotoxic T lymphocytes (MP-CTL) were generated by the stimulation of CD3(+) T lymphocytes from HLA-A2(+) individuals with either autologous mature dendritic cells or T2 cells pulsed with a cocktail of these four peptides.

RESULTS:

The peptide cocktail did not compromise tumor antigen-specific activity of CTLs. MP-CTLs displayed increased total, effector memory (CCR7(-)CD45RO(+)), and activated (CD69(+)) CD3(+)CD8(+) T lymphocytes. In addition, MP-CTL showed IFN-γ production, cell proliferation, and cytotoxicity against HLA-A2(+) multiple myeloma cells, including cells of HLA-A2(+) patients with multiple myeloma. Importantly, MP-CTLs showed specific responses in functional assays to each relevant peptide but not to an irrelevant HLA-A2-specific CMV pp65 (NLVPMVATV) peptide.

CONCLUSIONS:

These results highlight the potential therapeutic application of vaccination with a cocktail of HLA-A2-specific peptides to induce CTLs with a broad spectrum of immune responses against multiple myeloma antigens.

PMID:
22753586
PMCID:
PMC3839582
DOI:
10.1158/1078-0432.CCR-11-2776
[Indexed for MEDLINE]
Free PMC Article

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