Manufacturing time and cost create two of the biggest challenges to making cell therapies available to more patients. Scientists at San Diego-based Artiva Biotherapeutics hope to change that with cancer and autoimmune therapies based on natural killer (NK) cells from donors—allogeneic—that are not genetically modified.
Antibodies can connect natural killer (NK) cells with their target, inducing them to attack and kill the targeted cell. Killing cancer cells or the immune system’s B cells can be used to fight cancer or autoimmune diseases, respectively. “Even without engineering NK cells, we can leverage antibodies for targeting and for enhancing the activity of those antibodies and improve their ability to kill cancer cells or B cells,” says Fred Aslan, MD, Artiva’s president and CEO. “Plus, there has been a lot of data showing that allogeneic NK cells don’t generate graft-versus-host disease as compared to T cells.”
Cytokine release syndrome
In addition, NK cells have not been seen to trigger serious cytokine release syndrome, which can be caused by therapies based on T cells. Last, using natural NK cells avoids any concerns that might arise from engineered ones.
Rather than starting with an idea and worrying about how to make a product later, Aslan says, “One thing that set us apart from everyone else is that our approach has been what we call manufacturing first.” To accomplish that, Artiva uses a process that was developed by GC Cell in South Korea.
From one umbilical-cord unit, Artiva makes thousands of vials of cryo-preserved NK cells. “In each one of those vials, there’s a billion NK cells,” Aslan says. “So, from one umbilical-cord unit, we can make trillions of cells.” That’s crucial because NK cells don’t persist and don’t expand like T cells. So, NK-based therapies need a large number of cells, and patients need multiple doses, where each can contain billions of cells.
Given that the NK cells are not engineered, Artiva selects umbilical cord units that contain cells with the desired genetic variants. In brief, these variants create NK cells that are better at fighting cancer or autoimmune diseases.
Although Artiva is still in early clinical phases of developing off-the-shelf treatments based on NK cells, Aslan is already thinking ahead. “Part of our innovation going forward is making sure that our manufacturing processes are using the most scalable reagents, and we’re using a very closed process to minimize any variability,” he says. “We’re working with different components of the manufacturing process to see if we can further increase our yield.”