GK-1 peptide reduces tumor growth, decreases metastatic burden, and increases survival in a murine breast cancer model. Issue 42 (9th October 2017)

• Record Type: Journal Article
• Authors: Torres-García, D.; Pérez-Torres, A.; Manoutcharian, K.; Orbe, U.; Servín-Blanco, R.; Fragoso, G.; Sciutto, E.
• Is Part Of: Vaccine. Volume 35:Issue 42(2017)
• Page Start: 5653
• Page End: 5661
• Publication Date: 2017-10-09
• Subjects: BC breast cancer -- aa amino acid -- SS saline solution -- H&E hematoxylin and eosin -- SD standard deviation -- MAM metastasis-associated macrophages -- MDSC myeloid-derived suppressor cells; Breast cancer -- Metastasis -- Immunotherapy -- Primary tumor -- GK-1; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2017.08.060
• Languages: English
• ISSNs: 0264-410X

Abstract

Highlights: An anti-neoplastic effect of GK-1 in a murine breast cancer model is proposed. The GK-1 effect relies on increasing IL-12 and necrosis at the primary tumor. GK-1 reduces the concentration of pro-metastatic chemokines at the lungs. Abstract: GK-1 is a parasite-derived peptide adjuvant of 18 amino acid-length that enhances T-cell function and increases survival in B16-F10 melanoma tumor-bearing mice. This study was designed to evaluate in vivo the antitumor efficacy of GK-1 on 4T1 mouse mammary carcinoma. BALB/c mice with palpable primary tumors were weekly intravenously injected three times with saline solution or three different concentrations (10, 50, or 100 μg per mouse) of GK-1. GK-1 significantly increased lifespan ( p < 0.0001) and reduced the primary tumor weight ( p = 0.014) and volume ( p < 0.0001) with respect to control mice, with no statistically significant differences among GK-1 doses. At the primary tumor, we found increased necrotic areas associated with a reduction in tumor mass, as well as an increase in the antitumor cytokine IL-12. Especially encouraging is the ability of GK-1 to reduce the number of lung metastasis ( p = 0.006) disregarding the dose used. The participation of IL-6 in metastasis development and the decreased levels of CCL-2, CCL-3, TNF-α, CXCL-9, GM-CSF, and b-FGF found in lungs of GK-1-treated mice is discussed. Our study supports the effectiveness of GK-1 as an antineoplastic agent that merits further exploration in combination with other therapeutic approaches in future translational studies.