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

We previously established safety and immunogenicity of a p53 synthetic long peptides (p53-SLP registered ) vaccine. In the current trial, we investigated whether combination of interferon-alpha (IFN-[alpha]) with p53-SLP registered is both safe and able to improve the induced p53-specific IFN-[gamma...

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Published in:International journal of cancer 2013-04, Vol.132 (7), p.1581-1591
Main Authors: Zeestraten, Eliane CM, Speetjens, Frank M, Welters, Marij JP, Saadatmand, Sepideh, Stynenbosch, Linda FM, Jongen, Rogier, Kapiteijn, Ellen, Gelderblom, Hans, Nijman, Hans W, Valentijn, ARob PM, Oostendorp, Jaap, Fathers, Lorraine M, Drijfhout, Jan W, van de Velde, Cornelis JH, Kuppen, Peter JK, van der Burg, Sjoerd H, Melief, Cornelis JM
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Language:English
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Summary:We previously established safety and immunogenicity of a p53 synthetic long peptides (p53-SLP registered ) vaccine. In the current trial, we investigated whether combination of interferon-alpha (IFN-[alpha]) with p53-SLP registered is both safe and able to improve the induced p53-specific IFN-[gamma] 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 registered together with IFN-[alpha]. 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 registered only. Toxicity of p53-SLP registered vaccination in combination with IFN-[alpha] 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-[alpha] significantly improved the frequency of p53-specific T cells in IFN-[gamma] 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 registered 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 registered vaccination combined with IFN-[alpha] injection is safe and capable of inducing p53-specific immunity. When compared to a similar trial with p53-SLP registered vaccination alone the combination was found to induce significantly more IFN-[gamma] producing p53-specific T cells. What's new? Immunotherapy against p53 is a promising strategy to treat colorectal cancers with otherwise poor prognosis as the tumor suppressor protein is mutated in almost half of these cancers, which allows the differentiation between tumor and non-tumor cells. In the current study, the authors vaccinated metastatic colorectal cancer patients with synthetic long p53 peptides (p53-SLP registered ) in combination with interferon-alpha (IFN-[alpha]). They found the combination treatment safe and efficient as significantly more IFN-[gamma] producing p53-specific T-cells were produced compared to treatment wit
ISSN:0020-7136
1097-0215
DOI:10.1002/ijc.27819