Exosomes in Cancer
The emerging field of cancer exosome biology represents fertile ground for the development of novel therapeutics. Exosomes are small, secreted vesicles approximately 30 to 300nm in diameter that are secreted by all human cell types into body fluids. Exosomes are loaded with specific subsets of cellular proteins, RNAs, lipids, and carbohydrates that can be taken up by surrounding cells or distant cells through circulation. Exosomes appear to transport much or all of the extracellular RNA communication that occurs in humans, including the transfer of functional miRNAs, lncRNAs, and mRNAs from one cell to another, allowing them to transmit signals by altering a cell’s gene expression patterns.
Most importantly, it is now clear that cancer cells release gene and other signals to surrounding healthy cells and through circulation to distant cells that support their growth and metastasis. Cancer cells appear to have a distinct role in exosome biology, as cancer cells release far more exosomes than their normal counterparts. We have found that cancer cells also appear to avidly take up stroma-derived exosomes, and even signal stromal cells to modulate the composition of their exosomes in ways that ultimately promote cancer cell growth and invasiveness.
We have demonstrated that we are able to deliver high levels of specific miRNA, including widely known cancer disruptive targets such as miR195, directly to cancer cells. We have shown using in vivo models that our miRNA-loaded exosomes inhibit cancer growth and prolongs lifespan. We have focused on exploiting a cancer cell’s natural pre-disposition to taking up large quantities of certain types of exosomes to insert microRNAs that will disrupt the cancer growth instruction set.
Repeated dosing of animals with miRNA-loaded exosomes did not elicit any overt signs of inflammation, toxicity, or other indications of intolerance.