In a proof-of-principle study in mice, scientists at Johns Hopkins Medicine report the creation of a specialized gel that acts like a lymph node to successfully activate and multiply cancer-fighting immune system T-cells. The work puts scientists a step closer, they say, to injecting such artificial lymph nodes into people and sparking T-cells to fight disease.
In the past few years, a wave of discoveries has advanced new techniques to use T-cells — a type of white blood cell — in cancer treatment. To be successful, the cells must be primed, or taught, to spot and react to molecular flags that dot the surfaces of cancer cells. The job of educating T-cells this way typically happens in lymph nodes, small, bean-shaped glands found all over the body that house T-cells. But in patients with cancer and immune system disorders, that learning process is faulty, or doesn’t happen.
To address such defects, current T-cell booster therapy requires physicians to remove T-cells from the blood of a patient with cancer and inject the cells back into the patient after either genetically engineering or activating the cells in a laboratory so they recognize cancer-linked molecular flags.
One such treatment, called CAR-T therapy, is costly and available only at specialized centers with laboratories capable of the complicated task of engineering T-cells. In addition, it generally takes about six to eight weeks to culture the T-cells in laboratories and, once reintroduced into the body, the cells don’t last long in the patient’s body, so the effects of the treatment can be short-lived.
The new work, reported April 10 in the journal Advanced Materials, is a bid by Johns Hopkins scientists to find a more efficient way of engineering T-cells.
“We believe that a T-cell’s environment is very important. Biology doesn’t occur on plastic dishes; it happens in tissues,” says John Hickey, a Ph.D. candidate in biomedical engineering at the Johns Hopkins University School of Medicine and first author of the study report.
To make the engineered T-cells’ environment more biologically realistic, Hickey — working with his mentors Hai-Quan Mao, Ph.D., associate director of the Johns Hopkins Institute for NanoBioTechnology and Jonathan Schneck, M.D., Ph.D., professor of pathology, medicine and oncology at the Johns Hopkins University School of Medicine — tried using a jelly-like polymer, or hydrogel, as a platform for the T-cells. On the hydrogel, the scientists added two types of signals that stimulate and “teach” T-cells to hone in on foreign targets to destroy.
In their experiments, T-cells activated on hydrogels produced 50 percent more molecules called cytokines, a marker of activation, than T-cells kept on plastic culture dishes.
Because hydrogels can be made to order, the Johns Hopkins scientists created and tested a range of hydrogels, from the very soft feel of a single cell to the more rigid quality of a cell-packed lymph node.
“One of the surprising findings was that T-cells prefer a very soft environment, similar to interactions with individual cells, as opposed to a densely packed tissue,” says Schneck.
More than 80 percent of T-cells on the soft surface multiplied themselves, compared with none of the T-cells on the most firm type of hydrogel.
When the Johns Hopkins team put T-cells onto a soft hydrogel, they found that the T-cells multiplied from just a few cells to about 150,000 cells — plenty to use for cancer therapy — within seven days. By contrast, when the scientists used other conventional methods to stimulate and expand T-cells, they were able to culture only 20,000 cells within seven days.
In the next set of experiments, the scientists injected the T-cells engineered in either the soft hydrogels or the plastic culture dishes into mice implanted with melanoma, a lethal form of skin cancer. Tumors in mice with T-cells cultured on hydrogels remained stable in size, and some of the mice survived beyond 40 days. By contrast, tumors grew in most of the mice injected with T-cells cultured in plastic dishes, and none of these mice lived beyond 30 days.
“As we perfect the hydrogel and replicate the essential feature of the natural environment, including chemical growth factors that attract cancer-fighting T-cells and other signals, we will ultimately be able to design artificial lymph nodes for regenerative immunology-based therapy,” says Schneck, a member of the Johns Hopkins Kimmel Cancer Center.
The Latest on: Artificial lymph nodes
via Google News
The Latest on: Artificial lymph nodes
- Machine Learning and Feature Selection Applied to SEER Data to Reliably Assess Thyroid Cancer Prognosison March 20, 2020 at 3:08 am
Utilizing historical clinical datasets to guide future treatment choices is beneficial for patients and physicians. Machine learning and feature selection algorithms (namely, Fisher’s discriminant ...
- What doctors and health experts are doing to stay well right nowon March 17, 2020 at 5:55 am
"We have many lymph nodes in the abdomen, so it’s also particularly good to focus around this ... and very cold plunge pools and I’m addicted! The heat from the banya creates an artificial ‘fever’ and ...
- Nanoengineering Approaches to the Design of Artificial Antigen-presenting Cellson March 16, 2020 at 5:00 pm
Acellular artificial antigen-presenting cells (aAPCs) are micro- or nano ... with improved in vivo performance due to easy access to draining lymph nodes, and suitability for intravenous injection.
- Can we live to be 1,000 years old? How science is on a mission to slow ageing and extend the human lifespanon March 15, 2020 at 5:00 am
The fund has spent millions of dollars supporting US biotech companies such as Freenome, which is using machine learning to develop technology for early-stage detection of colorectal cancer; LyGenesis ...
- Immune Recognition and Rejection of Allogeneic Skin Graftson March 14, 2020 at 5:00 pm
The transplantation of allogeneic skin grafts is associated with a potent ... vessels and infiltrate the recipient's draining lymph nodes where they present donor antigens via two mechanisms ...
- New weapon to fight allergies discoveredon March 2, 2020 at 11:16 pm
The cells then migrate from the lymph nodes - where they are stored - to ... New Delhi, March 03 (ANI): Artificial intelligence can improve the precision of sleep medicines, resulting in more ...
- US specialist whose husband died of cancer says we need to stop toxic treatments and get smarton February 26, 2020 at 10:40 am
“Wave after wave of researchers keep trying to develop drugs using these artificial systems and ... By then, the cancer had spread to her lymph nodes, but body scans suggested it hadn’t ...
- UAH research could have broad implications for immunotherapy and cancer treatmenton February 20, 2020 at 11:35 pm
Research into engineering artificial organs that mimic the functions of human lymph nodes at The University of Alabama in Huntsville (UAH) has garnered one of its professors a $507,777 National ...
- UAH professor honored for work ‘priming’ immune cellson February 20, 2020 at 9:29 am
“When our body is infected with bacteria or viruses, some special immune cells are ‘primed’ within the lymph nodes to fight ... “Second, using the artificial lymph node, we can discover ...
- Testicular Cancer: Surgeryon October 15, 2017 at 1:54 pm
If you wish, you can have your healthcare provider insert an artificial testicle at a later time. This is surgery to remove the lymph nodes behind the abdomen ... possible side effects that men with ...
via Bing News