Exosome-based cancer vaccine for prevention of lung cancer

Abstract

Background: Our earlier work has shown that a unique stem cell-based vaccine that comprises of murine embryonic stem cells (ESCs) and murine fibroblasts expressing the immunostimulant granulocytemacrophage colony stimulating factor (GM-CSF) successfully protects mice from the outgrowth of an implantable form of murine lung cancer. The use of live ESCs raises the potential risks of inducing teratomas and autoimmunity. We have attempted to improve the safety and utility of this prophylactic vaccine by employing exosomes derived from murine ESCs engineered to produce GM-CSF (ES-exo/GM-CSF vaccine). Methods:We have previously reported that ES-exo/GM-CSF immunization does protect mice from the outgrowth of an implantable form of murine lung cancer. Here, we have investigated the cancer prevention efficacy of ES-exo/GM-CSF vaccine in an experimental metastasis model of murine lung cancer, in which Lewis lung carcinoma (LLC) cells were administered into female C57BL/6 mice (8 weeks of age) through tail vein injection and subsequently LLC tumors were established in lungs.Results: Our objective is to test the anti-cancer efficacy of ES-exo/GM-CSF vaccine in a mouse model of metastatic lung cancer. Our studies indicate that vaccination of mice with ES-exo/GM-CSF vaccine inhibited the growth of metastatic lung tumors. ES-exo/GM-CSF vactionation reduced lung tumor burden from

Encapsulation and assessment of therapeutic cargo in engineered exosomes: a systematic review

“…Exosomes are also being investigated as cancer vaccines with advantages over traditional chemotherapies such as higher specificity, controllability, and free of toxicity [ 17 – 19 ]. A recent study demonstrated that, when co-administered with a cancer vaccine, exosomes released by M1-polarized macrophages could boost vaccine immunogenicity and anti-tumor immune responses in mouse models, which shines light on the therapeutic potential of engineered exosomes to develop optimized anti-cancer vaccines [ 20 ].…”

Extracellular vesicles in nanomedicine and regenerative medicine: A review over the last decade

“…Although cancer vaccine designs are frequently suboptimal, they have shown promising results in clinical activity, especially in increasing overall survival [ 258 ]. A prophylactic vaccine was developed by using exosomes derived from murine ESCs (embryonic stem cells) to produce ESC-exo/GM-CSF (granulocyte-macrophage colony-stimulating factor), the studies showed that the advance of metastatic lung tumors was inhibited in mice vaccinated with ES-exo/GM-CSF vaccine [ 259 ]. In addition, vaccines based on exosomes originating from dendritic cells have been confirmed to be simpler in terms of cost-effectiveness and management compared to dendritic cell vaccines [ 260 ].…”

The multifaceted role of extracellular vesicles (EVs) in colorectal cancer: metastasis, immune suppression, therapy resistance, and autophagy crosstalk

“…More recently, Meng et al demonstrated immunization with embryonic stem cells (ESCs)-derived EVs expressing GM-CSF prevents lung metastasis effectively in Lewis lung carcinoma-challenged mice compared to non-vaccinated tumor-bearing mice. Further, immunization with ESC-EV/GM-CSF circumvents tumor-infiltrating Tregs, MDSCs, and TAMs and provokes cytokine secretion from intratumor CD8 + T cells [ 257 ].…”