SCV-07 treatment leads to alterations in VEGF, MIF, IL-1alpha, and MIP-1beta levels in patients with head and neck cancer

Introduction: Serum was collected before and after chemoradiation therapy from head and neck cancer (HNC) patients enrolled in a phase 2, randomized, double-blind, dose-ranging, placebo-controlled trial designed to test the safety, tolerability and efficacy of an immunomodulatory peptide, gamma-D-glutamyl-L-tryptophan (SCV-07) as an intervention for oral mucositis (OM). Results of the trial demonstrated that the high dose of SCV-07 (0.1 mg/kg daily on days of radiation) was safe and effective in attenuating the course of OM. The objective of this study was to determine if the administration of high dose SCV-07 affected detectable levels of peripheral blood cytokines that may be involved in the host response to chemoradiation therapy for HNC.

Experimental Procedures: Samples were analyzed via multiplex (Affymetrix Procarta cytokine assay), evaluating 35 proteins expected to be affected by SCV-07, which has been shown to stimulate a Th1 cytokine profile and to inhibit IL-6 dependent STAT3 signaling. For each of the 35 proteins, the null hypothesis “average subject protein value in high-dose regimen subjects equals average subject protein value in placebo regimen subjects” was tested against the alternative hypothesis “average subject protein value in high-dose regimen subjects does not equal average subject protein value in placebo regimen subjects.” A two tail test (=0.05) was used as there was no a priori knowledge of a relationship between protein levels and treatment regimen. Unequal population variances were assumed as the samples were not assumed to be random draws from the same population. The dataset analyzed 26 subjects given the high dose SCV-07 regimen and 23 subjects given placebo.

Summary of Results: MIF, MIP-1beta, and VEGF were found to be significantly higher (p < 0.049, p < 0.049, p < 0.015 respectively) in high dose SCV-07 treated individuals compared to placebo, whereas IL-1alpha was found to be significantly lower (p < 0.045) in high dose SCV-07 treated individuals compared to placebo.

Conclusions: SCV-07 treatment leads to increases in circulation of some immune-related cytokines (MIF, MIP-1beta, and VEGF) and leads to a decrease in another (IL-1alpha). These results can be used to better understand SCV-07's mechanism of action, and to follow biomarkers during future clinical trials evaluating SCV-07.

Basic Research, Epigenetics, Immunology, Noncoding RNAs, Tumor Microenvironment, Metastasis, Target Identification, Validation, Lead Discovery, and Optimization