Immunotherapy: Football-shaped Particles Against Cancer


Researchers at Johns Hopkins have succeeded in making flattened, football-shaped artificial particles that impersonate immune cells. These football-shaped particles seem to be better than the typical basketball-shaped particles at teaching immune cells to recognize and destroy cancer cells in mice.

"The shape of the particles really seems to matter because the stretched, ellipsoidal particles we made performed much better than spherical ones in activating the immune system and reducing the animals' tumors," according to Jordan Green, assistant professor of biomedical engineering at the Johns Hopkins University School of Medicine and a collaborator on this work.

"Unfortunately, traditional chemotherapy drugs do not know healthy cells from tumor cells, but immune system cells recognize this difference. We wanted to enhance the natural ability of T-cells to find and attack tumor cells," says Jonathan Schneck, professor of pathology, medicine and oncology.

In their experiments, Schneck and Green's team exploited the well-known immune system interaction between antigen-presenting cells (APC) and T-cells. APCs "swallow" invaders and then display on their surfaces chewed-up protein pieces from the invaders along with molecular "danger signals." When circulating T-cells interact with APCs, they learn that those proteins come from an enemy, so that if the T-cells see those proteins again, they divide rapidly to create an army that attacks and kills the invaders.

According to Schneck, to enhance this natural process, several laboratories have made various types of "artificial APCs" — tiny inanimate spheres "decorated" with pieces of tumor proteins and danger signals. These are then often used in immunotherapy techniques in which immune cells are collected from a cancer patient and mixed with the artificial APCs. When they interact with the patient's T-cells, the T-cells are activated, learn to recognize the tumor cell proteins and multiply over the course of several days. The immune cells can then be transferred back into the patient to seek out and kill cancer cells.

The cell-based technique has had only limited success and involves risks due to growing the cells outside the body, Green says. These downsides sparked interest in the team to improve the technique by making biodegradable artificial APCs that could be administered directly into a potential patient and that would better mimic the interactions of natural APCs with T-cells. "When immune cells in the body come in contact, they are not doing so like two billiard balls that just touch ever so slightly," explains Green. "Contact between two cells involves a significant overlapping surface area. We thought that if we could flatten the particles, they might mimic this interaction better than spheres and activate the T-cells more effectively."

When the researchers compared typical spherical and football-shaped particles — both coated with tumor proteins and danger signals at equivalent densities and mixed with T-cells in the laboratory — the T-cells multiplied many more times in response to the stretched particles than to spherical ones. In fact, by stretching the original spheres to varying degrees, they found that, up to a point, they could increase the multiplication of the T-cells just by lengthening the "footballs."

When the particles were injected into mice with skin cancer, the T-cells that interacted with the elongated artificial APCs, versus spherical ones, were also more successful at killing tumor cells. Schneck says that tumors in mice that were treated with round particles reduced tumor growth by half, while elongated particles reduced tumor growth by three-quarters. Even better, he says, over the course of a one-month trial, 25 percent of the mice with skin cancer being treated with elongated particles survived, while none of the mice in the other treatment groups did.; Source: John Hopkins Medicine