-
Categories
-
Pharmaceutical Intermediates
-
Active Pharmaceutical Ingredients
-
Food Additives
- Industrial Coatings
- Agrochemicals
- Dyes and Pigments
- Surfactant
- Flavors and Fragrances
- Chemical Reagents
- Catalyst and Auxiliary
- Natural Products
- Inorganic Chemistry
-
Organic Chemistry
-
Biochemical Engineering
- Analytical Chemistry
-
Cosmetic Ingredient
- Water Treatment Chemical
-
Pharmaceutical Intermediates
Promotion
ECHEMI Mall
Wholesale
Weekly Price
Exhibition
News
-
Trade Service
The CRISPR-Cas9 complex (blue and yellow) can precisely cut DNA (red).
A small clinical trial showed that researchers could use CRISPR gene editing to alter immune cells so that they could recognize mutated proteins
specific to human tumors.
These cells can then be safely released in the body, finding and destroying their targets
.
It's the first attempt to combine two hot areas of cancer research: gene editing to create personalized treatments, and modifying immune cells called T cells to better target tumors
.
The method was tested
in 16 patients with solid tumors, including the breast and colon.
"This is probably the most complex treatment ever tried clinically," said study co-author Antoni Ribas
, a UCLA cancer researcher and physician.
"We're trying to build an army
with patients' own T cells.
"
The findings were published in the journal Nature and presented
Nov.
10 at the Society for Cancer Immunotherapy meeting in Boston, Massachusetts.
Ribas and his colleagues set out to sequence DNA from blood samples and tumor living tissue to look for mutations
found in tumors but not in blood.
Everyone in the trial has to do this
.
"The mutations in each cancer are different, and although there are some common mutations, they are only a minority
.
"
The researchers then used algorithms to predict which mutations might trigger a response from T cells, a type of white blood cell that roams the body looking for the wrong cells
.
"If [T cells] see something that isn't normal, they kill it," said
Stephanie Mandl, chief scientific officer of PACT Pharmaceuticals in South San Francisco, Calif.
, and lead author of the study.
"But in the cancer patients we see in the clinic, at some point, the immune system seems to lose its fight and the tumor grows
.
"
After a series of analyses to confirm their findings, validate their predictions, and design a protein called the T cell receptor, which recognizes tumor mutations, the researchers took blood samples from each participant and inserted the receptor into their T cells
using CRISPR genome editing.
Each participant then had to take a drug to reduce the number of immune cells they produced, which were then infused into engineered cells
.
"It's an extremely complex manufacturing process," said
Joseph Fraietta, who designed T-cell cancer therapies at the University of Pennsylvania in Philadelphia.
In some cases, the entire process took more than a year
.
Each of the 16 participants received engineered T cells
with three different targets.
Afterward, they found that the edited cells circulated in their bloodstream and were in higher concentrations near the tumor than unedited cells
.
One month after treatment, 5 participants were in stable condition, meaning their tumors were not growing
.
Only two people experienced side effects
that could be due to the activity of the edited T cells.
Although the effect of this treatment is low, Ribas said, the researchers used relatively small doses of T cells to determine the safety
of this approach.
"We just need to fight harder next time
," he said.
As researchers investigate ways to accelerate the development of therapies, engineered cells will be cultured in vitro for less time and may be more active
when injected.
"The technology is going to get better and better
," Fraietta said.
Engineered T cells, known as CAR-T cells, have been approved to treat some blood and lymphoma cancers, but solid tumors pose a particular challenge
.
CAR - T cells are only effective
against proteins expressed on the surface of tumor cells.
This protein can be found in many blood and lymphoma cancers, meaning there is no need to engineer new T-cell receptors
for every cancer patient.
But Fraietta says common surface proteins
have not yet been found in solid tumors.
Solid tumors provide a physical barrier for T cells, which must circulate in the blood, reach the tumor, and then penetrate into the tumor to kill cancer cells
.
Tumor cells also sometimes suppress the immune response, promoting rapid growth
by releasing immunosuppressive chemical signals and depleting the local nutrient supply.
Fraietta said: "The environment around the tumor is like a sewer
.
Once T cells reach this site, their function decreases
.
”
With this initial proof of concept, Mandl and her colleagues hope to be able to design T cells that not only recognize cancer mutations, but also be more active
near tumors.
Mandel said there are several possible ways to enhance the resilience of T cells, for example, by removing receptors that respond to immunosuppressive signals, or by tweaking their metabolism to make it easier for them to find a source of
energy in the tumor environment.
Avery Posey, who studies cell and gene therapy for cancer treatment at the University of Pennsylvania in Philadelphia, said that such elaboration may be feasible
thanks to recent technological advances using CRISPR to edit T cells.
"It became very efficient," he said
.
"We're going to see very sophisticated approaches
to immune cell engineering over the next decade.
"
