title: Addition of interferon-α to the p53-SLP® vaccine results in increased production of interferon-γ in vaccinated colorectal cancer patients: a phase I/II clinical trial.
abstract: We previously established safety and immunogenicity of a p53 synthetic long peptides (p53-SLP®) vaccine. In the current trial, we investigated whether combination of interferon-alpha (IFN-α) with p53-SLP® is both safe and able to improve the induced p53-specific IFN-γ response. Eleven colorectal cancer patients successfully treated for metastatic disease were enrolled in this study. Of these, nine patients completed follow-up after two injections with p53-SLP® together with IFN-α. Safety and p53-specific immune responses were determined before and after vaccination. Furthermore, cryopreserved PBMCs were compared head-to-head to cryopreserved PBMCs obtained in our previous trial with p53-SLP® only. Toxicity of p53-SLP® vaccination in combination with IFN-α was limited to Grade 1 or 2, with predominantly small ongoing swellings at the vaccination site. All patients harbored p53-specific T cells after vaccination and most patients showed p53-specific antibodies. Compared to the previous trial, addition of IFN-α significantly improved the frequency of p53-specific T cells in IFN-γ ELISPOT. Moreover, in this trial, p53-specific T cells were detectable in blood samples of all patients in a direct ex vivo multiparameter flowcytometric assay, opposed to only 2 of 10 patients vaccinated with p53-SLP® only. Finally, patients in this trial displayed a broader p53-specific immunoglobulin-G response, indicating an overall better p53-specific T-helper response. Our study shows that p53-SLP® vaccination combined with IFN-α injection is safe and capable of inducing p53-specific immunity. When compared to a similar trial with p53-SLP® vaccination alone the combination was found to induce significantly more IFN-γ producing p53-specific T cells.
authors.affiliation: Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Eliane C M
authors.initials: EC
authors.lastname: Zeestraten
authors.forename: Frank M
authors.initials: FM
authors.lastname: Speetjens
authors.forename: Marij J P
authors.initials: MJ
authors.lastname: Welters
authors.forename: Sepideh
authors.initials: S
authors.lastname: Saadatmand
authors.forename: Linda F M
authors.initials: LF
authors.lastname: Stynenbosch
authors.forename: Rogier
authors.initials: R
authors.lastname: Jongen
authors.forename: Ellen
authors.initials: E
authors.lastname: Kapiteijn
authors.forename: Hans
authors.initials: H
authors.lastname: Gelderblom
authors.forename: Hans W
authors.initials: HW
authors.lastname: Nijman
authors.forename: A Rob P M
authors.initials: AR
authors.lastname: Valentijn
authors.forename: Jaap
authors.initials: J
authors.lastname: Oostendorp
authors.forename: Lorraine M
authors.initials: LM
authors.lastname: Fathers
authors.forename: Jan W
authors.initials: JW
authors.lastname: Drijfhout
authors.forename: Cornelis J H
authors.initials: CJ
authors.lastname: van de Velde
authors.forename: Peter J K
authors.initials: PJ
authors.lastname: Kuppen
authors.forename: Sjoerd H
authors.initials: SH
authors.lastname: van der Burg
authors.forename: Cornelis J M
authors.initials: CJ
authors.lastname: Melief
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols; D000998:Antiviral Agents / Q000627:therapeutic use*; D019496:Cancer Vaccines / Q000627:therapeutic use*; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008113:Liver Neoplasms / Q000276:immunology / Q000556:secondary / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011379:Prognosis; D011994:Recombinant Proteins / Q000627:therapeutic use; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D000998:Antiviral Agents; D019496:Cancer Vaccines; D016898:Interferon-alpha; D010446:Peptide Fragments; D011994:Recombinant Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D011092:Polyethylene Glycols; D007371:Interferon-gamma; C100416:peginterferon alfa-2a