Addition of interferon-alpha to the p53-SLP (R) vaccine results in increased production of interferon-gamma in vaccinated colorectal cancer patients: A phase I/II clinical trial

作者：Zeestraten Eliane C M; Speetjens Frank M; Welters Marij J P; Saadatmand Sepideh; Stynenbosch Linda F M; Jongen Rogier; Kapiteijn Ellen; Gelderblom Hans; Nijman Hans W; Valentijn A Rob P M; Oostendorp Jaap; Fathers Lorraine M; Drijfhout Jan W; van de Velde Cornelis J H; Kuppen Peter J K; van der Burg Sjoerd H; Melief Cornelis J M^*

来源：International Journal of Cancer, 2013, 132(7): 1581-1591.

DOI：10.1002/ijc.27819

• p53
• immunotherapy
• colon
• colorectal
• cancer
• vaccine
• synthetic long peptides
• immune monitoring
• therapeutic
• IFN-a

We previously established safety and immunogenicity of a p53 synthetic long peptides (p53-SLP (R)) vaccine. In the current trial, we investigated whether combination of interferon-alpha (IFN-a) with p53-SLP (R) is both safe and able to improve the induced p53-specific IFN-? 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 (R) together with IFN-a. 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 (R) only. Toxicity of p53-SLP (R) vaccination in combination with IFN-a 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-a significantly improved the frequency of p53-specific T cells in IFN-? 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 (R) 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 (R) vaccination combined with IFN-a injection is safe and capable of inducing p53-specific immunity. When compared to a similar trial with p53-SLP (R) vaccination alone the combination was found to induce significantly more IFN-? producing p53-specific T cells.

• 出版日期2013-4-1