In recent years, exosomes have emerged as promising and sensitive cancer biomarkers for use in disease diagnosis. Exosomes released from cancer cells after entering the circulation are transported in biological fluids along with their functional cargoes. Profiling the nucleic acids of exosomes derived from cancer cells by ultrasensitive next-generation sequencing and proteins by large-scale high-throughput proteomics can help us in early cancer detection, therapeutic stratification, and monitoring patient-specific responses to various cancer therapies.
This has been proven true particularly for urologic tumors, and now the FDA has granted Fast Track approvals for two exosome diagnostics. Exosome-based diagnostics have an advantage over existing diagnostic tests for cancer because of their stability in body fluids. This characteristic of exosomes allows specific cancer-derived proteins and nucleic acids to be preserved.
Furthermore, cancer cells tend to secrete more exosomes than the normal cells and exosomes shed by cancer cells can initiate and propagate cancer to other parts in the body, causing metastasis. For example, it has been shown that the exosomes expressing PD-L1 secreted by metastatic melanomas help the tumor to evade immune surveillance. Thus, evaluation of exosomal PD-L1 content has been proposed to stratify patients for therapy with anti-PD-1 antibodies, a promising treatment for metastatic melanoma.
Exosomes can also be stable, biocompatible, and reliable engineered nanocarriers to deliver therapeutics to disease-affected target cells. In a number of studies, exosomes have been used as anticancer therapies by delivering therapeutic miRNAs, proteins, and drugs. To date, drug delivery with exosomes has been utilized for the treatment of breast, pancreatic, lung, and prostate cancers and glioblastoma. Furthermore, surface modification of exosome membranes with ligands or proteins tends to increase the homing efficiency of exosomes loaded with therapeutics.
The Shift from Cell Therapy to Exosome Therapy
An increasing number of cell therapy companies are now shifting their focus to include exosome products. Most of these companies are seeking to exploit the inherent therapeutic effects of naïve (naturally produced) exosomes derived from stem cells, although some have ventured into the world of engineered exosomes.
Other exosome companies have been established by experts with a background in the delivery of biological therapeutics, such as DNA, RNA, or proteins. Instead of using exosomes in their naïve form, these companies tend to focus on engineering exosomes to deliver a therapeutic payload, such as DNA, RNA, or a protein to a target cell type.
For example, Capricor Therapeutics, established in 2005, was pursuing a cell therapy treatment for the rare genetic disorder called Duchenne muscular dystrophy, using cardiosphere-derived cells (CDCs). However, in 2018, the company discovered that, in Duchenne, the therapeutic effect of CDCs was particularly due to the exosomes released by CDCs. Therefore, Capricor is now studying CDC exosomes (CAP-2003) as a “next generation” regenerative medicine for Duchenne and other diseases of inflammation and fibrosis (meaning, scarring).
Aruna Biomedical, another stem cell company, has an even longer history with stem cells. Founded in 2003, the company has specialized in producing human neural stem cells for sale to researchers. However, in 2017 Aruna started pursuing exosomes released by the neural stem cells as a potential treatment for stroke. In October 2019, Aruna received funding from U.S. National Institutes of Health (NIH) to support research and development, and ultimately, started human clinical trials in 2021.
In contrast, Aegle Therapeutics was founded in 2013 with a focus on exosomes from the beginning. The company’s founder had some frustrating experience with his research on the clinical applications of MSCs for burns and wounds. Thankfully, his team discovered that the MSC-derived exosomes demonstrate similar regenerative functionality to their parent cells, opening the potential for “cell-free” therapy. Thus, Aegle now develops exosome therapies for skin conditions such as burns, scarring, and epidermolysis bullosa. The company has commenced formal clinical trials using exosomes derived from MSCs for the treatment of dystrophic epidermolysis bullosa (“DEB”), a rare pediatric skin blistering disorder.
Cynata Therapeutics was founded in 2011 centered around a unique Cymerus™ technology that can provide induced pluripotent stem cell (iPSC) derived MSCs. Shortly thereafter in 2013, it became clear that the company’s MSCs could also be used to manufacture therapeutic exosomes. Thus, the original founder of Cynata founded another company, Exopharm, in late 2013. Exopharm’s exosome product candidate, Plexaris, has now entered human clinical trials in Australia for wound healing.
Founded from the beginning with a focus on exosomes, Codiak Biosciences has also entered into clinical trials, using exosomes as vehicles to deliver biological cargo to target cells. The company’s engineered anticancer exosomes are based on the research from MD Anderson Cancer Center at the University of Texas. The Oxford-based Evox has also moved into exosomes as a means to improve gene therapy.
As more and more exosome clinical trials get underway during the next few years and sector leaders start reporting their clinical trial results, the exosome field is likely to grow. The next few years will undoubtedly see dynamic change, and hopefully, the first world’s first approval of an exosome therapeutic. What other exosome advances have attracted your attention? Share them in the comments below.
To learn more about this rapidly expanding market, view the “The Global Exosome Market – Market Size, Forecast, Trials and Trends, 2022.”
