Work

Antitumoral effectiveness and safety of intravenous versus subcutaneous administration of immunomodulatory peptide GK-1 in a murine breast cancer model

Year: 2025

Type: article

Abstract: A bstract GK-1 is a safe and effective molecule with high antimetastatic activity against murine breast and skin cancer. GK-1 treatment enhances cytotoxic response of CD8 + lymphocytes against the tumor and modifies the oxidative stress in the tumor. This study was designed to compare the antitumor efficacy of GK-1 by subcutaneous (SC) versus intravenous (IV) route of administration in the 4T1 mouse mammary carcinoma model and to extend its innocuity in heart and kidney, key tissues for observing damage induced by anticancer drugs and immunotherapy. BALB/c female mice were injected orthotopically with 1000 4T1 cells. When palpable primary tumors of about 1 mm 3 were detected, GK-1 (5 mg/kg) was administered IV or SC weekly for 21 days. Tumor growth and mouse weight were monitored weekly. The primary tumor weight and volume, the number of lung metastases, and programmed cell death protein 1 (PD-1) expression were recorded after 28 days of starting treatment. Kidney, heart, spleen, serum, and blood samples from naïve mice were obtained to evaluate the safety of GK-1 administration by measuring the degree of damage to these tissues with specific cytotoxic markers. Subcutaneous or intravenous administration of GK-1 significantly increased the lifespan of mice and significantly reduced the primary tumor weight and volume and the number of lungs macrometastases. GK-1 reduced the expression of PD-1 in tumor-infiltrating lymphocytes in mice regardless of the route of immunization used, which is especially encouraging. No evidence of damage to kidney or heart tissues was detected in the tumor-free mice. This study supports that subcutaneous GK-1 administered, has an efficacy non-inferior to intravenous administration, well-tolerated with a similar safety profile and therefore offers a less invasive valid treatment alternative. • The subcutaneous and intravenous treatment of GK-1 had equal antitumoral effect in a breast cancer model. • GK-1 treatment reduces the expression of PD-1 on tumor infiltrating lymphocytes. • GK-1 is not immunogenic; therefore, it does not cause antibody immune-mediated adverse effects such as renal or cardiac damage in tumor-free mice. • GK-1 does not increase reactive oxygen species in tumor-free mice.

Source: Vaccine

DOI: 10.1016/j.vaccine.2025.126814