Researchers from the University of California, Los Angeles (UCLA) have unveiled a new tool consisting of graphene oxide with attached antibodies that allows engineered CAR-T cells to more closely mimic the natural interactions between immune cells, effectively boosting the therapy’s cancer-fighting attributes. This innovation, reported recently in the journal Nature Nanotechnology, looks poised to overcome one of the hurdles to CAR-T treatment effectiveness: the fact that current methods for activating T cells in the body don’t closely resemble the natural environment in which they interact with, an important population of immune cells, which is crucial to spurring T cells to increase their activity to fight cancer.
“Our interface bridges the gap between the laboratory and actual conditions inside the body, allowing us to gain insights much more relevant to real-world biological processes,” said senior author Yu Huang, PhD, a professor of engineering at UCLA, who noted that this approach has the potential to be applied in other areas as well, including tissue engineering and regenerative medicine.
In their research, the UCLA team anchored two specific antibodies onto graphene oxide. In lab studies they showed that over a 12-day period, the graphene-antibodies platform aided in a 100-fold-plus increase in T cell expansion in a blood cell culture. Further, the investigators showed that their new platform increased the efficiency of engineering the CAR-T cells five-fold over current methods. Their research also details discoveries of the technology’s ability to activate several biochemical pathways that are vital to T cell signaling and function that enable this highly improved rate of T cell growth.
“We’ve developed an exciting new approach to boosting the effectiveness of T cell therapies,” said co-corresponding author Lili Yang, a professor of microbiology, immunology and molecular genetics at UCLA. “Our method enhanced the potency and efficiency of these cells in ways that weren’t possible with traditional methods. This is particularly important for CAR-T cell therapy, where the strength and proliferation of T cells makes a significant difference in patient outcomes.”
While their graphene-antibodies platform importantly boosts the effectiveness of CAR-T therapy, their finding of its ability to boost production of CAR T cells during the engineering process was also important. Current methods for engineering the therapeutic cells in the lab before they are re-infused into the patient require the addition of autocrine interleukin-2, also called IL-2. In their experiments, the researchers discovered that the platform stimulated production of IL-2, which may make it possible to streamline the production process by eliminating the need to add IL-2.
Currently, the costs associated with producing a personalized CAR-T cell therapy are very high, often exceeding $370,000 per patient due to the complexity of engineering the cells, as well as the expense of other components needed for production, such as IL-2. This new discovery could eventually help mitigate the high cost.
“We got very excited when we discovered that our method can overcome the dependence on external IL-2 supplementation,” said co-first author Enbo Zhu, PhD, a postdoc in the Huang lab. “We confirmed that our rational design for mimicking an important immunological interaction is on the right track. It encourages us to dive deeper into developing its applications in CAR-T cell therapy.”
