Bioengineering Ligands To Fight Cancer And Regenerate Neuron
Our human body is made up of cells, and the biological processes of these cells are regulated by protein messengers known as ligands that bind to receptors on the cell surface
Now a team of researchers led by Jennifer Cochran at Stanford has tweaked a ligand in slightly different ways to produce two surprising results. One set of alterations inhibited lung tumor growth, while a different tweak to the same protein caused neuronal cells to regenerate.
The researchers did the experiments on mice, rats, and human cells that model actual diseases and published their results in the Proceedings of the National Academy of Sciences. The studies are far from being tested in humans, but the results show how close the scientists are in repairing the body’s protein-based control mechanisms to help vital organs heal themselves.
These proteins can one day be used to treat cancers, disorders like atherosclerosis and osteoporosis, and neurodegenerative disease.
Cochran and her team of researches are involved in studying the interactions between receptors and ligands and how it can be engineered to create potent therapeutic agents.
Ligands are made of amino acids linked together and folded into three-dimensional shapes. A ligand fits the right receptor, just like a key fits a lock.
The researchers can change the lineup of amino acids in a ligand using sophisticated molecular engineering techniques to get the desired results like a ligand that fits better in the receptor than the endogenous agonist, called superagonist. Superagonists might transmit signals that instruct cells to grow more robustly.
The same technique can also be used to turn ligands into antagonists, that can fit into the ligand and block the signal, retarding functions like cell growth.
Now the scientists are bioengineering ligands to fight cancer and regenerate neurons.
Cohran published a paper last year showing how an engineered version of the receptor protein CNTFR, helped stop lung tumor growth in rodents. She collaborated with Alejandro Sweet-Cordero, a cancer researcher at UC San Francisco, for this particular study.
Now, Jun Kim, a graduate student, engineered the ligand CLCF1, which binds to the CNFTR receptor. Kim turned the ligand into a superagonist by making one set of amino acid alterations in CLCF1. These superagonists increased the messaging signals in injured neuronal cells and promoted the growth of axons that transmit nerve simples. These engineered ligands encouraged the injured ligands to regenerate themselves.
Also, Kim showed that they could turn this same ligand into a potent antagonist by introducing a few additional amino acid alterations to CLCF1. And this antagonist inhibited the growth of lung tumors in mice.
Cochran has been developing novel engineered proteins as therapeutic candidates for regenerative medicine and oncology applications. Her most advanced therapies for kidney and ovarian cancer are now in human trials.
Cochran is optimistic that engineered ligands and receptors will continue to prove to be a promising class of drugs to fight illness and maintain health.
Editor’s Note; Bioengineering Ligands To Fight Cancer And Regenerate Neuron, altering CLCF1 ligand