Piñón-Zárate Gabriela, Hernández-Téllez Beatriz, Ramírez-Cortés Ariel, Jarquín-Yáñez Katia, Sampedro-Carrillo Enrique A, Herrera-Enríquez Miguel A, Cárdenas-Monroy Christian A, Castell-Rodríguez Andrés E
Laboratory of Immunotherapy and Tissue Engineering, Faculty of Medicine, National Autonomous University of Mexico, Mexico City 04510, Mexico.
Laboratory of Genetics, National School of Forensic Sciences, National Autonomous University of Mexico, Mexico City 04510, Mexico.
Pharmaceutics. 2025 Jul 19;17(7):932. doi: 10.3390/pharmaceutics17070932.
One current cancer treatment is immunotherapy, in which tumor antigens (such as MAGE) or adjuvants (such as CpGs) can be used to induce the destruction of tumor cells by the immune system; however, the therapeutic response is generally weak. Therefore, it is necessary to develop a strategy that increases the immune response induced by tumor antigens and CpGs. We propose the coupling of tumor antigens and adjuvants to chitosan (Cs) microparticles to improve the immune response against cancer, as these microparticles can activate the innate immune response when recognized by macrophages and dendritic cells (DCs). Cs microparticles coupled with CpGs and tumor antigens were constructed with the emulsification method; then, their morphology, in vitro biological effect on DCs, and therapeutic effect in a murine melanoma model were analyzed. The Cs microparticles showed a rounded morphology and a size of approximately 5 μ; in addition, they were not cytotoxic in in vitro assays and induced the production of IFNα. Finally, in the murine model of melanoma, treatment with Cs microparticles coupled to MAGE or CpGs reduced the tumor growth rate and increased both survival and the presence of cell death areas in the tumor parenchyma in contrast to the control group. The results suggest that treatment with Cs microparticles coupled to tumor antigen and/or CpGs can be considered a promising strategy in the field of immunotherapy based on the use of biomaterials.
目前的一种癌症治疗方法是免疫疗法,其中肿瘤抗原(如黑色素瘤相关抗原)或佐剂(如CpG)可用于诱导免疫系统破坏肿瘤细胞;然而,治疗反应通常较弱。因此,有必要开发一种策略来增强由肿瘤抗原和CpG诱导的免疫反应。我们提出将肿瘤抗原和佐剂偶联到壳聚糖(Cs)微粒上,以改善针对癌症的免疫反应,因为这些微粒在被巨噬细胞和树突状细胞(DCs)识别时可激活先天免疫反应。采用乳化法构建了偶联CpG和肿瘤抗原的Cs微粒;然后,分析了它们的形态、对DCs的体外生物学效应以及在小鼠黑色素瘤模型中的治疗效果。Cs微粒呈现圆形形态,大小约为5μm;此外,它们在体外试验中无细胞毒性,并可诱导IFNα的产生。最后,在黑色素瘤小鼠模型中,与对照组相比,用偶联MAGE或CpG的Cs微粒治疗可降低肿瘤生长速率,并提高生存率以及增加肿瘤实质中细胞死亡区域的出现。结果表明,基于生物材料的使用,用偶联肿瘤抗原和/或CpG的Cs微粒进行治疗可被视为免疫疗法领域一种有前景的策略。