Please use this identifier to cite or link to this item: http://hdl.handle.net/20.500.12779/6565
Title: Phase I trial of thymidylate synthase poly-epitope peptide (TSPP) vaccine in advanced cancer patients
Authors: Cusi, Maria Grazia
Botta, Cirino
Pastina, Pierpaolo
Rossetti, Maria Grazia
Dreassi, Elena 
Guidelli, Giacomo Maria
Fioravanti, Antonella
Martino, Elodia Claudia
Gandolfo, Claudia
Pagliuchi, Marco
Basile, Assunta
Carbone, Salvatore Francesco
Ricci, Veronica
Micheli, Lucia
Tassone, Pierfrancesco
Tagliaferri, Pierosandro
Pirtoli, Luigi
Correale, Pierpaolo
Keywords: Cancer vaccine; CTLs; Immune response; Immunotherapy; Phase Ib trial; Cancer Research; Oncology; Immunology; Immunology and Allergy
Issue Date: 2015
Project: None 
Journal: CANCER IMMUNOLOGY, IMMUNOTHERAPY
Abstract: 
Thymidylate synthase (TS) poly-epitope peptide (TSPP) is a 27-mer peptide vaccine containing the amino acidic sequences of three epitopes with HLA-A2.1-binding motifs of TS, an enzyme overexpressed in cancer cells, which plays a crucial role in DNA repair and replication. Based on the results of preclinical studies, we designed a phase Ib trial (TSPP/VAC1) to investigate, in a dose escalation setting, the safety and the biological activity of TSPP vaccination alone (arm A) or in combination with GM-CSF and IL-2 (arm B) in cancer patients. Twenty-one pretreated metastatic cancer patients, with a good performance status (ECOG ≤ 1) and no severe organ failure or immunological disease, were enrolled in the study (12 in arm A, nine in arm B) between April 2011 and January 2012, with a median follow-up of 28 months. TSPP resulted safe, and its maximal tolerated dose was not achieved. No grade 4 toxicity was observed. The most common adverse events were grade 2 dermatological reactions to the vaccine injection, cough, rhinitis, fever, poly-arthralgia, gastro-enteric symptoms and, to a lesser extent, moderate hypertension and hypothyroidism. We detected a significant rise in auto-antibodies and TS-epitope-specific CTL precursors. Furthermore, TSPP showed antitumor activity in this group of pretreated patients; indeed, we recorded one partial response and seven disease stabilizations (SD) in arm A, and three SD in arm B. Taken together, our findings provide the framework for the evaluation of the TSPP anti-tumor activity in further disease-oriented clinical trials.
Description: 
75283
URI: http://hdl.handle.net/20.500.12779/6565
ISSN: 0340-7004
DOI: 10.1007/s00262-015-1711-7
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