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

Abstract

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.

• Authors: 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, Pierosandro Tagliaferri
• Journal: Oncotarget (Oncotarget) Vol. 9 Issue 29 Pg. 20539-20554 (Apr 17 2018) ISSN: 1949-2553 [Electronic] United States
• PMID: 29755670 (Publication Type: Journal Article)