Cancer therapy poised for rapid advances
SAN DIEGO, California: The remarkable cancer treatment that uses a patient’s own immune cells to treat their cancer has saved a growing number of people who were close to death. But sometimes this treatment, known as CAR T cell therapy, fails, and that has perplexed researchers.
That puzzle is being pieced together, and more effective variations on this therapy are on the way, a pioneer in this therapy said Thursday at a symposium at the UC San Diego Moores Cancer Center.
A deeper understanding of how - ter genetic engineering methods for these cells are fueling the advances, said medical doctor Carl June of the University of Pennsylvania. Besides the T cell therapy, which is the best known, other immune cells called natural killer cells and macrophages are also being brought into service.
Not only will the treatments get more effective, but it now appears possible that the current cost of several hundred thousand dollars could in the long term drop dramatically, June said. He presented information from research yet to be published pointing to those advances.
Just one engineered cell can proliferate and defeat a cancer, June said, citing results from one patient. That patient was infused with many genetically engineered immune cells. One of those cells proliferated more than all others, pounds of tumor cells.
Engineering one cell is far less expensive than growing a batch of cells, June said, and it is conceivable that could bring down the cost of therapy to that of a regular blood transfusion. That cost varies between several hundred to a few thousand dollars.
Automation will also help, June said in an interview after his speech.
“It’s very cheap to do this with machines, rather than it being done it by hand, which it is right now with scientists and technicians,” June said.
However, it’s unclear how difficult it will be to replicate that in the interview. Safety is also an issue — uncontrolled proliferation is a hallmark of cancer. So more research is needed to understand how this process takes place and to minimize risks.
In his speech, June gave an example of a known danger. Another cancer patient received a batch of engineered immune cells that contained one “rogue” cell. That cell proliferated and killed the patient.
“It also is the first real proof of the tumor stem cell hypothesis,” June said.
Genetic changes
That hypothesis says that the most dangerous cancer cells have undergone genetic changes that make them in some ways resemble stem cells. They aggressively proliferate and are the hardest to kill.
This was shown by examining the patient’s cancer cells.
“We could show at the time he died, every single cell had the [ge descendants of one cell,” June said.
Another discovery is that in patients that fail CAR T cell therapy, their immune cells often have be This T cell exhaustion also occurs in untreated HIV patients.
What that means is that the cells are unsuitable for therapy, June said. Moreover, certain types of cancers are more likely to produce this exhaustion than others.
It may be possible to rescue these exhausted cells with appropriate genetic modifications, June said. That’s being tested in a new clinical trial for prostate cancer that has overcome hormone therapy, socalled “castrate resistant” prostate cancer, where the cancer keeps growing even when the amount of testosterone in the body is reduced to very low levels.
In a second clinical study, the groundbreaking gene editing technique called CRISPR is being used to create better, more precisely engineered CAR T cells. This is now being tested in four cancers, including multiple myeloma and melanoma.
Both studies are recruiting pa - tion at The prostate cancer study can be found under number NCT03089203. The multiple myeloma and melanoma study can be found under the number NCT03399448.F.