Immune monitoring of patients treated with a whole-cell melanoma vaccine engineered to express 4-1BBL

Roni Engelstein, Sharon Merims, Galit Eisenberg, Jonathan Cohen, Stephen Frank, Tamar Hamburger, Shoshana Frankenburg, Ilan Ron, Ruth Isacson, Tal Grenader, Hanna Steinberg, Cyrille J. Cohen, Tamar Peretz, Michal Lotem*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

CD8 lymphocytes are mandatory mediators of tumor regression. To enhance their specific antitumor activity, we aimed to improve a melanoma cell-based vaccine by transfecting it with 4-1BB ligand, a costimulatory and immune modulatory molecule. Thirty-four American Joint Committee on Cancer (AJCC) stage IIB-IV patients were vaccinated with a melanoma antigen-rich cell line engineered to express HLA-A2 and 4-1BBL (M20/A2/BBL). Twelve serially recruited patients were monitored for interferon γ expression and CD107a mobilization before and after vaccination. Thirty-three patients remained alive, with an estimated mean overall survival of 26.2 months. No grade 3-4 adverse events were encountered. Immune monitoring detected an increase in circulating antimelanoma CD8 T cells in 9 of 12 patients, which were significantly stimulated by the parental melanoma, reflecting a relevant antitumor response. The results from this study show that the costimulatory 4-1BB ligand fortifies an antigen-rich melanoma cell line with enhanced antigen-specific stimulation of CD8 T cells. The use of a costimulatory molecule as part of a vaccine confers a selective increase of T-cell subsets with antimelanoma reactivity, which in some cases were characterized for their epitope specificity.

Original languageEnglish
Pages (from-to)321-328
Number of pages8
JournalJournal of Immunotherapy
Volume39
Issue number8
DOIs
StatePublished - 19 Oct 2016
Externally publishedYes

Funding

FundersFunder number
Ministry of Science, Technology & Space, Israel & Deutsches Krebsforschungszentrum
Perlstein Family Fund
Advanced Medical Research Foundation
Melanoma Research Alliance
Dr. Miriam and Sheldon G. Adelson Medical Research Foundation
German Cancer Research Center
Rosetrees Trust
Deutsche Forschungsgemeinschaft
Israel Cancer Association

    Keywords

    • 4-1BB ligand
    • CD107a
    • Immune monitoring
    • Interferon-gamma
    • Melanoma vaccine

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