In an early clinical safety testing in mice, researchers at Johns Hopkins Medicine report the development of a specialized jelly material that can mimic a lymph node. It aims to effectively spark and reproduce cancer-fighting immune system T-cells. The study brings scientists closer, as they say, to administering such artificial lymph nodes into patients and activating T-cells to combat disease.
The Role Of Lymph Nodes
In recent years, a wave of medical breakthroughs has refined techniques that use T-cells – a type of white blood cell – in treating cancer. To be successful, the cells must be taught or primed to detect and respond to molecular flags that trace the surfaces of cancer cells.
The job of programming immune cells this way usually happens in lymph nodes. Located in different parts of the body, lymph nodes are tiny, bean-shaped glands that house T-cells. In patients with immune system disorders and cancer, however, this natural learning process is either faulty or does not occur at all.
Current T-cell booster treatment targets such defects, but it requires the physician to extract T-cells from the blood of a cancer patient. After activating the cells in a laboratory or genetically engineering them so they identify cancer-related molecular flags, the doctor will reintroduce the cells into the patient.
One such technique, called CAR-T therapy, is expensive and available only at specialized clinics with laboratories capable of the complex job of engineering T-cells. Furthermore, it typically takes around six to eight weeks to culture these cells in the lab. Once injected into the patient, the cells don’t last long in the body, so the results of the treatment may not last long.
Creating A Suitable Environment For T-cells
The new work, published April 10 in the journal Advanced Materials, is a bid by Johns Hopkins researchers to look for a more sustainable way of engineering the cancer-fighting cells. John Hickey, first author of the report and a Ph.D. candidate of biomedical engineering at the Johns Hopkins University School of Medicine, explains that the T-cells environment is crucial. He says, “Biology doesn’t occur on plastic dishes; it happens in tissues.”
Hickey worked with his mentors Jonathan Schneck, M.D., Ph.D., professor of oncology, pathology, and medicine at the Johns Hopkins University School of Medicine and Hai-Quan Mao, Ph.D., associate director of the Johns Hopkins Institute for NanoBioTechnology. They tried to make the setting of engineered T-cells more biologically realistic by using a hydrogel (a gel-like polymer) as a platform for the cells. On this substance, the researchers added two kinds of signals that teach and stimulate T-cells to hone in on foreign invaders to destroy.
In their experiments, they found out that T-cells triggered on hydrogels formed 50 percent more cytokines, a molecule that marks activation, than the ones kept on plastic culture dishes. The results show that the immune cells prefer a very soft environment, mimicking interactions with individual cells.
The team is testing different types of hydrogel to create a perfect solution. This is supposed to replicate the essential feature of the chemical growth factors and natural setting that attract T-cells. Ultimately, their goal is to design artificial lymph nodes for cancer therapy.