title: Triple peptide vaccination as consolidation treatment in women affected by ovarian and breast cancer: Clinical and immunological data of a phase I/II clinical trial.
abstract: Vaccination with priming and expansion of tumour reacting T cells is an important therapeutic option to be used in combination with novel checkpoint inhibitors to increase the specificity of the T cell infiltrate and the efficacy of the treatment. In this phase I/II study, 14 high-risk disease-free ovarian (OC) and breast cancer (BC) patients after completion of standard therapies were vaccinated with MUC1, ErbB2 and carcinoembryonic antigen (CEA) HLA-A2+-restricted peptides and Montanide. Patients were subjected to 6 doses of vaccine every two weeks and a recall dose after 3 months. ECOG grade 2 toxicity was observed at the injection site. Eight out of 14 patients showed specific CD8+ T cells to at least one antigen. None of 4 patients vaccinated for compassionate use showed a CD8 activation. An OC patient who suffered from a lymph nodal recurrence, showed specific anti-ErbB2 CD8+ T cells in the bulky aortic lymph nodes suggesting homing of the activated T cells. Results confirm that peptide vaccination strategy is feasible, safe and well tolerated. In particular OC patients appear to show a higher response rate compared to BC patients. Vaccination generates a long-lasting immune response, which is strongly enhanced by recall administrations. The clinical outcome of patients enrolled in the trial appears favourable, having registered no deceased patients with a minimum follow-up of 8 years. These promising data, in line with the results of similar studies, the high compliance of patients observed and the favourable toxicity profile, support future trials of peptide vaccination in clinically disease-free patients who have completed standard treatments.
authors.affiliation: Department of Gynecology, Obstetrics and Urology, 'Sapienza' University of Rome, Policlinico Umberto I, 00161 Rome, Italy.
authors.forename: Morena
authors.initials: M
authors.lastname: Antonilli
authors.affiliation: Department of Experimental Medicine, 'Sapienza' University of Rome, Policlinico Umberto I, 00161 Rome, Italy.
authors.forename: Hassan
authors.initials: H
authors.lastname: Rahimi
authors.affiliation: Department of Experimental Medicine, 'Sapienza' University of Rome, Policlinico Umberto I, 00161 Rome, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Visconti
authors.affiliation: Department of Experimental Medicine, 'Sapienza' University of Rome, Policlinico Umberto I, 00161 Rome, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Napoletano
authors.affiliation: Department of Gynecology, Obstetrics and Urology, 'Sapienza' University of Rome, Policlinico Umberto I, 00161 Rome, Italy.
authors.forename: Ilary
authors.initials: I
authors.lastname: Ruscito
authors.affiliation: Department of Experimental Medicine, 'Sapienza' University of Rome, Policlinico Umberto I, 00161 Rome, Italy.
authors.forename: Ilaria Grazia
authors.initials: IG
authors.lastname: Zizzari
authors.affiliation: Department of Experimental Medicine, 'Sapienza' University of Rome, Policlinico Umberto I, 00161 Rome, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Caponnetto
authors.affiliation: Department of Experimental Medicine, 'Sapienza' University of Rome, Policlinico Umberto I, 00161 Rome, Italy.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Barchiesi
authors.affiliation: Department of Gynecology, Obstetrics and Urology, 'Sapienza' University of Rome, Policlinico Umberto I, 00161 Rome, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Iadarola
authors.affiliation: Department of Experimental Medicine, 'Sapienza' University of Rome, Policlinico Umberto I, 00161 Rome, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Pierelli
authors.affiliation: Department of Experimental Medicine, 'Sapienza' University of Rome, Policlinico Umberto I, 00161 Rome, Italy.
authors.forename: Aurelia
authors.initials: A
authors.lastname: Rughetti
authors.affiliation: Department of Gynecology, Obstetrics and Urology, 'Sapienza' University of Rome, Policlinico Umberto I, 00161 Rome, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Bellati
authors.affiliation: Department of Gynecology, Obstetrics and Urology, 'Sapienza' University of Rome, Policlinico Umberto I, 00161 Rome, Italy.
authors.forename: Pierluigi Benedetti
authors.initials: PB
authors.lastname: Panici
authors.affiliation: Department of Experimental Medicine, 'Sapienza' University of Rome, Policlinico Umberto I, 00161 Rome, Italy.
authors.forename: Marianna
authors.initials: M
authors.lastname: Nuti
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology; D002272:Carcinoembryonic Antigen / Q000008:administration & dosage* / Q000276:immunology; D018572:Disease-Free Survival; D005260:Female; D005434:Flow Cytometry; D015789:HLA-A2 Antigen / Q000235:genetics / Q000276:immunology; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008875:Middle Aged; D018396:Mucin-1 / Q000008:administration & dosage* / Q000276:immunology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000008:administration & dosage* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D019496:Cancer Vaccines; D002272:Carcinoembryonic Antigen; D015789:HLA-A2 Antigen; D018396:Mucin-1; D010446:Peptide Fragments; D018719:Erb-b2 Receptor Tyrosine Kinases; C060192:MUC1 protein, human; C508053:ERBB2 protein, human