Chimeric antigen receptor (CAR) T cells, developed in the 1990s, are a genetically engineered type of T cell that can target a specific cancer. Now, scientists at Purdue University say they've made improvements in this strategy--overcoming the several limitations of traditional CAR-T therapy.
Purdue professor of chemistry Philip Low and his team presented their findings at the American Association for Cancer Research meeting in New Orleans last month.
T cells are a type of immune cell that recognizes and clears the body of invading cells or pathogens, like cancer. They are fine-tuned by the immune system in order to specifically target and kill these foreign invaders--but cancer cells may respond by jumping these safety barriers.
CAR-T therapy was therefore proposed and has been recently used for cancer treatment. It has been hailed for its promising remission rates after early stage clinical trials for acute lymphoblastic leukemia.
"The problem is that the traditional engineered T-cell treatment can be too effective, sometimes killing tumor cells too fast and triggering a toxic reaction in a patient, and sometimes not stopping once the tumor has been destroyed and continuing to seek out and destroy healthy cells important to bodily functions," Low said in a university news release. "We have found a potential way to control the engineered immune cells to overcome the limitations posed by CAR T-cell therapy."
They did this by teaming up with Endocyte ($ECYT) scientist Haiyan Chu and designing CAR T cells that require activation by a small molecule adaptor before proceeding. In this way, they can carefully control the amount of active CAR T cells in the circulation.
So far, they have only tried the novel therapy in animal models, but when they tested it in mice they observed antitumor activity only when both the CAR T cells and the correct adaptor molecules were present.
Low believes it will allow clinicians to target multiple cancer subtypes at once. "Most tumors are heterogeneous and contain cancer cells that express different characteristics, including having different tumor-specific proteins on their surface," he said in the release. "The cancer-targeting molecule on the adaptor we designed can be swapped out to target different molecules on other unrelated cancer cell surfaces. The idea is that a mixture of these adaptors can be given to a patient so that a single CAR T cell clone can be targeted to all of the relevant cancer subtypes in a patient."
"In the past a new CAR T cell had to be designed for each desired cancer target," Low said. "This system uses the same blind CAR T cell for all treatments. The adaptor molecule is what needs to be changed, and it is far easier to manipulate and swap pieces in and out of it than the T cells."
- here’s the release
Novartis-allied scientist at Penn creates a new CAR-T model for solid tumors
Baxalta dives into CAR-T with a $1.6B bet
Kite's CAR-T gets a 'breakthrough' tag with pivotal data on the way