Research Papers:

Systemic inflammatory status predict the outcome of k-RAS WT metastatic colorectal cancer patients receiving the thymidylate synthase poly-epitope-peptide anticancer vaccine

Pierpaolo Correale, Cirino Botta, Nicoletta Staropoli, Valerio Nardone, Pierpaolo Pastina, Cristina Ulivieri, Claudia Gandolfo, Tatiana Cosima Baldari, Stefano Lazzi, Domenico Ciliberto, Rocco Giannicola, Antonella Fioravanti, Antonio Giordano, Silvia Zappavigna, Michele Caraglia, Pierfrancesco Tassone, Luigi Pirtoli, Maria Grazia Cusi and Pierosandro Tagliaferri _

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Oncotarget. 2018; 9:20539-20554. https://doi.org/10.18632/oncotarget.24993

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Pierpaolo Correale1, Cirino Botta2, Nicoletta Staropoli3, Valerio Nardone4, Pierpaolo Pastina4, Cristina Ulivieri5, Claudia Gandolfo6, Tatiana Cosima Baldari5, Stefano Lazzi7, Domenico Ciliberto3, Rocco Giannicola1, Antonella Fioravanti8, Antonio Giordano9, Silvia Zappavigna10, Michele Caraglia9,10, Pierfrancesco Tassone2,3,10, Luigi Pirtoli4, Maria Grazia Cusi6 and Pierosandro Tagliaferri3

1Unit of Medical Oncology, Grand Metropolitan Hospital Bianchi Melacrino Morelli, Reggio-Calabria, Italy

2Medical Oncology Unit, AUO Mater Domini, Magna Graecia University, Catanzaro, Italy

3Department of Experimental and Clinical Medicine, Magna Graecia University , Catanzaro, Italy

4Unit of Radiotherapy, Department of Surgery, Medicine and Neurological Science, Siena University Hospital, Siena, Italy

5Department of Science of Life, Siena University, Siena, Italy

6Microbiology and Virology Unit, Department of Medical Biotechnology, Siena University, Siena, Italy

7Unit of Pathology, Department of Surgery, Medicine and Neurological Science, Siena University Hospital, Siena, Italy

8Unit of Rheumatology, Department of Clinical Medicine and Immunologic Sciences, University of Siena, Siena, Italy

9Department of Biotechnology, Temple University, Sbarro Foundation, Philadelphia, Pennsylvania, USA

10Department of Precision Medicine, University of Campania L. Vanvitelli, Naples, Italy

Correspondence to:

Pierosandro Tagliaferri, email: [email protected]

Pierpaolo Correale, email: [email protected]

Keywords: bio-markers; cancer vaccine; colorectal cancer; K-ras; thymidylate synthase

Received: August 24, 2017     Accepted: February 21, 2018     Published: April 17, 2018


TSPP is an anticancer poly-epitope peptide vaccine to thymidylate synthase, recently investigated in the multi-arm phase Ib TSPP/VAC1 trial. TSPP vaccination induced immune-biological effects and showed antitumor activity in metastatic colorectal cancer (mCRC) patients and other malignancies. Progression-free and overall survival of 41 mCRC patients enrolled in the study correlated with baseline levels of CEA, immune-inflammatory markers (neutrophil/lymphocyte ratio, CRP, ESR, LDH, ENA), IL-4 and with post-treatment change in p-ANCA and CD56dimCD16brightNKs (p < 0.04). A subset of 19 patients with activating k-ras mutations showed a different immune-inflammatory response to TSPP as compared to patients with k-ras/wt and a worse outcome in term of PFS (p = 0.048). In patients with k-ras/mut, inflammatory markers lost their predictive value and their survival directly correlated with the baseline levels of IL17/A over the median value (p = 0.01). These results provide strong hints for the design of further clinical trials aimed to test TSPP vaccination in mCRC patients.

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