Earlier this year we covered a very interesting and promising method of normal and tumor cell ex vivo propagation – so-called “conditional immortalization“:
Using Rho kinase (ROCK) inhibitor and feeder cell layer, Richard Schlegel’s group was able to propagate primary normal and malignant cells for long time. Basically, they created “stem cell-like” conditions. Interestingly, these conditions didn’t push selection for adult- or cancer stem cells from the tested tissues and cells didn’t undergo transformation.
Yesterday, I was happy to see a publication of the first “proof-of-principal” clinical case. The same group was able to propagate tumor cells from patient with rapidly progressing respiratory papillomatosis and test them for drug sensitivity. Customized therapy stopped cancer progression and the patient was stable for the last 15 months.
Drug testing methodology:
Cells isolated from the lung tumor and adjacent normal lung were plated in triplicate with J2 feeder cells in 24-well microtiter plates (BD Falcon) at 104 cells per well. Twenty-four hours later, the cells were treated with vehicle (dimethylsulfoxide), cidofovir, dihydroartemisinin, or vorinostat dissolved in dimethylsulfoxide at various concentrations for 48 hours. After removal of feeder cells, lung-cell viability was measured with the use of the CellTiter-Glo Luminescent Cell Viability Assay (Promega).
The whole procedure of tumor cell isolation/ propagation and drug testing takes 2 weeks.
Now, I’d like to quote some commentaries. From press-release:
Schlegel says teams of researchers from around the U.S. have visited his Georgetown lab to learn the “Georgetown Method,” a phrase coined by researchers who provided an accompanying commentary at the time the work was published.
Schlegel says, “Our first clinical application utilizing this technique represents a powerful example of individualized medicine,” but, he cautions, “It will take an army of researchers and solid science to figure out if this technique will be the advance we need to usher in a new era of personalized medicine.”
Comments of two Harvard’s stem cell experts:
For infections, it’s routine to grow bacteria from a patient in lab dishes to see which antibiotics work best, Dr. George Q. Daley of Children’s Hospital Boston and the Harvard Stem Cell Institute said in an email. “But this has never been possible with cancer cells because they don’t easily grow in culture,” he said.
“What could be more personalized than taking this person’s cell, growing it in culture, finding a drug to treat them and then treat them?” said Doug Melton, co-director of the Harvard Stem Cell Institute. The Georgetown method gives an answer quickly enough that it could save lives, he said.
I think, this is exciting news. One of the best examples of personalized medicine I’ve ever seen. It will be great to apply this method to the patients, who is deciding about enrollment in clinical trials. If investigational drug will not work on patient’s cells, probably there will be no point for enrollment. This scenario was actually tested in reported case. What if enrollment in oncology clinical trials will be highly selective, based on this method? Should we expect nearly 100% efficacy in Phase 2 then? I also wonder if we can use this approach in cellular immunotherapy.
