Understanding the Anti-Tumor Properties Mediated by the Synthetic Peptide GK-1

Abstract

Cancer exhibits adaptive features typical of complex systems, like resilience and robustness to environmental challenges through the emergent co-evolution of its components. These events promote carcinogenesis through dynamic interactions among numerous components and subsystems, including the immune system. During the past decade, our research group has provided substantial evidence that the peptide GK-1 has important immunomodulatory properties. In elderly mice, GK-1 acts as a potent adjuvant of the influenza vaccine through a mechanism that involves the activation of antigen-presenting cells (APCs) and an increased production of pro-inflammatory cytokines and chemokines (IFN-γ, TNFα, CCL2). To date, there is solid evidence supporting the antitumoral properties of GK-1 in murine cancer models. First, a lower occurrence and smaller size of spontaneous bronchiolar adenomas were found in elderly GK-1-treated mice compared to paired untreated mice. In two independent studies, GK-1 treatment reduced tumor growth and increased mouse survival in a murine model of melanoma and breast tumor. In the former model, a synergy between GK-1 and anti-PD-L1 treatment was observed, while in the latter, GK-1 alone controlled the metastatic burden. The effective activation of APCs induced by GK-1, restoring the antitumor-specific immunity, may underlie some of its antineoplastic effects.