Researchers at the University of Massachusetts Amherst have developed precise methods for targeting and manipulating specific cancer-causing proteins within malignant cells. These methods, published in the Journal of the American Chemical Society, are noted to have potential applications beyond cancer, extending to various immunological diseases. The principal investigator, Sankaran "Thai" Thayumanavan, stated that these are "platform technologies" applicable to a range of cellular diseases.
Cellular Protein Function
Cell membranes feature proteins that are critical for signaling pathways between the cell and its external environment. Damage or defects in these proteins can lead to uncontrolled cell division, characteristic of cancer, or enable malignant cells to evade the immune system. Approximately half of current therapeutic drugs target these membrane proteins.
"Shredding" Cancer-Causing Proteins (PolyTAC)
One developed approach focuses on identifying and destroying problematic proteins. Graduate students Ryan Lu and Jithu Krishna, along with their co-authors, discovered that physically indenting the cell surface at specific locations triggers the cell's natural internalization machinery. This process routes damaged surface proteins into the cell's waste disposal mechanism, where they are degraded.
The mechanism uses a "polymeric lysosome-targeting chimera," or PolyTAC. The PolyTAC consists of two components:
- An antibody, designed to recognize specific biomarker of the target protein.
- A polymer, which physically presses into the cell membrane to create the necessary indentation.
The antibody guides the PolyTAC to the specific protein, the polymer induces the dimple, and the cell subsequently processes and eliminates the protein.
Reprogramming Cancer Cells (ACDV)
Another platform, developed by Shuai Gong and Jingyi Qiu, is the "artificial cell-derived vesicle," or ACDV. This method aims to reprogram cancerous cells by delivering fully functional proteins to their surface, facilitating a return to normal function. The ACDV allows for the addition of proteins in real time, offering customizable therapies.
Potential applications include:
- Removing mechanisms that allow malignant cells to avoid immune system detection.
- Halting pathological cell division.
The team successfully demonstrated the technique by implanting four different proteins into cellular walls, suggesting adaptability for various therapeutic proteins. This method allows for the incorporation of functional proteins to modify cell surface display and overall cellular function.
Research Support
The National Institutes of Health supported the research for both methods. Much of the work occurred at the University of Massachusetts Amherst's Institute for Applied Life Sciences (IALS).