title: High immune response rates and decreased frequencies of regulatory T cells in metastatic renal cell carcinoma patients after tumor cell vaccination.
abstract: Our previously reported phase I clinical trial with the allogeneic gene-modified tumor cell line RCC-26/CD80/IL-2 showed that vaccination was well tolerated and feasible in metastatic renal cell carcinoma (RCC) patients. Substantial disease stabilization was observed in most patients despite a high tumor burden at study entry. To investigate alterations in immune responses that might contribute to this effect, we performed an extended immune monitoring that included analysis of reactivity against multiple antigens, cytokine/chemokine changes in serum and determination of the frequencies of immune suppressor cell populations, including natural regulatory T cells (nTregs) and myeloid-derived suppressor cell subsets (MDSCs). An overall immune response capacity to virus-derived control peptides was present in 100% of patients before vaccination. Vaccine-induced immune responses to tumor-associated antigens occurred in 75% of patients, demonstrating the potent immune stimulatory capacity of this generic vaccine. Furthermore, some patients reacted to peptide epitopes of antigens not expressed by the vaccine, showing that epitope-spreading occurred in vivo. Frequencies of nTregs and MDSCs were comparable to healthy donors at the beginning of study. A significant decrease of nTregs was detected after vaccination (p = 0.012). High immune response rates, decreased frequencies of nTregs and a mixed T helper 1/T helper 2 (T(H)1/T(H)2)-like cytokine pattern support the applicability of this RCC generic vaccine for use in combination therapies.
authors.affiliation: Laboratory of Tumor Immunology, LIFE Center, Ludwig Maximilians University, Munich, Germany. heike.pohla@med.uni-muenchen.de
authors.forename: Heike
authors.initials: H
authors.lastname: Pohla
authors.forename: Alexander
authors.initials: A
authors.lastname: Buchner
authors.forename: Birgit
authors.initials: B
authors.lastname: Stadlbauer
authors.forename: Bernhard
authors.initials: B
authors.lastname: Frankenberger
authors.forename: Stefan
authors.initials: S
authors.lastname: Stevanovic
authors.forename: Steffen
authors.initials: S
authors.lastname: Walter
authors.forename: Ronald
authors.initials: R
authors.lastname: Frank
authors.forename: Tim
authors.initials: T
authors.lastname: Schwachula
authors.forename: Sven
authors.initials: S
authors.lastname: Olek
authors.forename: Joachim
authors.initials: J
authors.lastname: Kopp
authors.forename: Gerald
authors.initials: G
authors.lastname: Willimsky
authors.forename: Christian G
authors.initials: CG
authors.lastname: Stief
authors.forename: Alfons
authors.initials: A
authors.lastname: Hofstetter
authors.forename: Antonio
authors.initials: A
authors.lastname: Pezzutto
authors.forename: Thomas
authors.initials: T
authors.lastname: Blankenstein
authors.forename: Ralph
authors.initials: R
authors.lastname: Oberneder
authors.forename: Dolores J
authors.initials: DJ
authors.lastname: Schendel
mesh_terms: D019496:Cancer Vaccines / Q000276:immunology*; D002292:Carcinoma, Renal Cell / Q000097:blood / Q000276:immunology* / Q000473:pathology* / Q000517:prevention & control; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood; D006801:Humans; D007109:Immunity / Q000276:immunology*; D007680:Kidney Neoplasms / Q000097:blood / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D018655:Lymphocyte Count; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D022423:Myeloid Cells / Q000276:immunology / Q000473:pathology; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D010455:Peptides / Q000276:immunology; D016019:Survival Analysis; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D013997:Time Factors; D016896:Treatment Outcome; D014611:Vaccination
chemical_list: D019496:Cancer Vaccines; D016207:Cytokines; D010455:Peptides