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.

Autor: 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.
Zdroj: International Journal of Cancer; Apr2013, Vol. 132 Issue 7, p1581-1591, 11p
Abstrakt: 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. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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