title: Immune Monitoring of Patients Treated With a Whole-Cell Melanoma Vaccine Engineered to Express 4-1BBL.
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.
authors: *Sharett Institute of Oncology, Hadassah Hebrew University Hospital ‡Department of Oncology, Shaare Zedek Medical Center, Jerusalem †Department of Oncology, Tel Aviv Sourasky Medical Center, Tel Aviv §Tumor Immunology and Immunotherapy Lab, Bar Ilan University, Ramat Gan, Israel.
authors: Roni
authors: R
authors: Engelstein
authors: Sharon
authors: S
authors: Merims
authors: Galit
authors: G
authors: Eisenberg
authors: Jonathan
authors: J
authors: Cohen
authors: Stephen
authors: S
authors: Frank
authors: Tamar
authors: T
authors: Hamburger
authors: Shoshana
authors: S
authors: Frankenburg
authors: Ilan
authors: I
authors: Ron
authors: Ruth
authors: R
authors: Isacson
authors: Tal
authors: T
authors: Grenader
authors: Hanna
authors: H
authors: Steinberg
authors: Cyrille J
authors: CJ
authors: Cohen
authors: Tamar
authors: T
authors: Peretz
authors: Michal
authors: M
authors: Lotem
mesh_terms: D053330:4-1BB Ligand / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D000368:Aged; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D005260:Female; D005818:Genetic Engineering; D015789:HLA-A2 Antigen / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008213:Lymphocyte Activation; D052118:Lysosomal-Associated Membrane Protein 1 / Q000378:metabolism; D008297:Male; D008545:Melanoma / Q000401:mortality / Q000628:therapy*; D008875:Middle Aged; D015166:Monitoring, Immunologic; D008991:Monitoring, Physiologic; D009367:Neoplasm Staging; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D053330:4-1BB Ligand; D019496:Cancer Vaccines; D015789:HLA-A2 Antigen; D052118:Lysosomal-Associated Membrane Protein 1; D007371:Interferon-gamma