The dialyzable leukocyte extract TransferonTM inhibits tumor growth and brain metastasis in a murine model of prostate cancer

Abstract

Prostate cancer (PCa) is the second most frequently diagnosed cancer in men worldwide. Dialyzed Leukocyte Extracts (DLEs) are heterogeneous mixtures of low-molecular-weight peptides that improve clinical responses in various diseases. Here, we analyzed the effects of TransferonTM, a commercial DLE with characterized active pharmaceutical ingredient and proven batch-to-batch reproducibility, in preclinical models of PCa. We employed v-Src-transformed murine prostate epithelial (PEC-Src) cells, which recapitulate the transcriptional profiles in human PCa, can be grown in immunocompetent mice, and consistently form bone and brain metastases. In vitro, TransferonTM did not induce cytotoxicity nor alterations in migration /invasion of PEC-Src cells. In vivo, TransferonTM reduced metastatic dissemination after intracardiac injection of PEC-Src and inhibited tumor growth of subcutaneous isotransplants. The antineoplastic effect of TransferonTM correlated with changes in tumor infiltration, increased serum concentrations of IL-12 and CXCL1, and reduced levels of VEGF. Our results suggest that the antineoplastic effect produced by TransferonTM is due to its immunomodulatory activity and not by a direct effect on cancer cells, and indicate that TransferonTM could be beneficial as adjuvant therapy in PCa patients.