RESUMEN
In our previous study, we reported the design and recombinant production of the p28-apoptin as a novel chimeric protein for breast cancer (BC) treatment. This study aimed to evaluate the inhibitory activity of the chimeric protein against BC cells in vitro and in vivo. We developed a novel multifunctional protein, consisting of p28, as a tumor-homing killer peptide fused to apoptin as a tumor-selective killer. The chimeric protein showed significantly higher toxicity in BC cell lines dose-dependently than in non-cancerous control cell lines. IC50 values were 1.41, 1.38, 6.13, and 264.49 µM for 4T1, MDA-MB-468, Vero, and HEK293 cells, respectively. The protein showed significantly enhanced uptake in 4T1 cancer cells compared with non-cancerous Vero cells. We also showed that the p28-apoptin chimeric protein binds significantly higher to human breast cancer tumor sections than the normal human breast tissue section. Also, significant apoptosis induction and tumor growth inhibition were observed in established tumor-bearing mice accompanied by a decreased frequency of metastases. Our results support that the chimeric protein has inhibitory activity in vitro and in vivo, making it a promising choice in targeted cancer therapy.
Asunto(s)
Antineoplásicos , Neoplasias de la Mama , Animales , Antineoplásicos/farmacología , Apoptosis , Neoplasias de la Mama/tratamiento farmacológico , Línea Celular Tumoral , Chlorocebus aethiops , Femenino , Células HEK293 , Humanos , Ratones , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/farmacología , Células VeroRESUMEN
This article provides a brief overview of DNA vaccines. First, the basic DNA vaccine design strategies are described, then specific issues related to the industrial production of DNA vaccines are discussed, including the production and purification of DNA products such as plasmid DNA, minicircle DNA, minimalistic, immunologically defined gene expression (MIDGE) and Doggybone™. The use of adjuvants to enhance the immunogenicity of DNA vaccines is then discussed. In addition, different delivery routes and several physical and chemical methods to increase the efficacy of DNA delivery into cells are explained. Recent preclinical and clinical trials of DNA vaccines for COVID-19 are then summarized. Lastly, the advantages and obstacles of DNA vaccines are discussed.