Synthetic T-Cells Could Bring Us Closer to Understanding Cancer
Making fake T cells might illuminate how the real ones work.
Much of what we know about trying to cure cancer involves T cells, the white blood cells that help lead our immune response to invaders. T cells fight against the flu, the common cold, and other infectious diseases with aplomb. But when it comes to cancer, they don’t seem to fight back.
There’s still a lot we don’t know about their behavior. They’re also hard to study—difficult to culture, expensive, and with a short shelf life.
“We can’t culture the primary T cells for a very long time, and we can’t freeze them,” Mohammad Mahdi Hasani-Sadrabadi, an assistant project scientist at UCLA’s Samueli School of Engineering, told The Daily Beast. “All immune cells are very delicate; we cannot keep them for very long.”
Dr. Hasani-Sadrabadi was inspired to create synthetic T cells after working on an NIH project exploring the interaction of immune cells and stem cells. One of the issues with implanting health donor stem cells in something like a bone marrow transplant is that the immune system can attack and destroy the stem cells as a foreign invader when in fact, they’re akin to allies.
The NIH project constantly required new extractions of T cells from human blood or animal tissues like the spleen or lymph nodes. But the issue went beyond the experimental time and expense of securing the needed T cells. The extraction process itself added additional variability, which then required more trials (to bring down the margin of error), and with that more time and expense.
That made synthetic T cells an intriguing option.
“Each time you extract T cells from animals or humans over and over and over there is a little variation which means you have to do the experiment a lot of times,” he said. “But dealing with a synthetic material, you can be sure that each time you get the same result.”
The synthetic T cells he’s created share the same physical characteristics as their natural kin, making them fine experimental fodder. Bringing down the expense and increasing availability will presumably widen the field of study, quickly increasing the breadth of knowledge about T cells.
“We wanted to have a kind of simplified model that can replicate the natural immune cells,” he says. “That’s the main rationale.”
There are a variety of T cells that perform different immunological functions. These include (but are not limited to) cytotoxic T cells or “killer” T cells which attack infections, memory T cells which are trained to respond to prior infection reappearing by rapidly multiplying, regulatory suppressor cells that dial back immune response and helper T cells, which are the immune system’s Paul Revere. These signaling cells are also called CD4+ T cells because of a protein they manifest on their surface.
It took Hasani-Sadrabadi’s UCLA team about 18 months to create their synthetic T cells, which look just like the real thing. Of course, they’re not living, so they’re not going to divide or change and respond to the environment by pumping out different cytokine proteins. Those proteins activate and alert other T cells or prompt other systemic changes depending on the protein released.
However synthetic T cells can be created to manifest particular proteins.
“The particles look exactly like real T cells, and their mechanical properties are the same,” Hasani-Sadrabadi said. “Their composition’s the same. They can deliver the cytokines and the same things that T cells generate, but they can not replicate or generate any change. They will only deliver whatever we put in there—it is not living matter.”
One of the key facets of the T cell is their flexibility, and it’s something that bioengineers have previously struggled with recreating. In order to reach tumors, T cells must penetrate tight spaces, shrinking down to a quarter of their normal size. They’re also capable of growing to nearly three times their size to help combat antigens that attack the immune system. The synthetic T cells have been able to replicate this elasticity.
The process of creating the synthetic particles involves making small biopolymer-based droplets in a highly controlled fashion. The resulting particle is clothed in a phospholipid like that of a human cellular membrane, then accessorized with exterior receptors, like little antennas, reading and responding to the surrounding chemical environment.
The UCLA lab can create entire T cell lines with different receptors for researchers to store and study. Different varieties of helper T cells release different proteins which respond to different environmental factors.
While natural T cells are obviously more mutable, this still offers the opportunity to potentially create entire galleries of different T cells, which could be a stand-in for the body’s in-the-moment dynamism.
That means synthetic T cells could even theoretically be used to amplify the body’s immune response by sending a squadron of synthetic T cells to the infection point to strengthen the signaling response. The team could also use the same process to create other types of immune cells—though synthetic killer T cells are probably very far off.
For the time being, Hasani-Sadrabadi’s lab’s primary focus is creating a workable synthetic T cell model that can open up research to more experimenters.
“We continue to try to make [synthetic T cells] as real as possible and the next success will be adding some simple machinery inside the cell in order to add protein production function to the T cells,” Hasani-Sadrabadi said, as opposed to the current situation where the desired protein is pre-loaded into the synthetic particle, which isn’t how real T cells actually perform.
“There’s still more to do to make this particle more realistic.”