Scientists at Johns Hopkins Medicine have created an artificial lymph node that shows promise in treating cancer, as demonstrated in a recent study involving mice and human cells. The newly developed lymph node, which is essentially a sac filled with immune system components, is implanted under the skin and serves as a learning hub and stimulator to educate T-cells in the immune system to identify and eliminate cancer cells. The study’s findings have been published, detailing the experiments conducted.The findings were recently published online and in the June 6 issue of Advanced Materials.
Lymph nodes, which are small glands found throughout the body in areas such as the neck, armpits, and groin, play a vital role in the immune systems of mammals, including mice and humans. There are hundreds of these nodes, allowing immune cells in one part of the body to quickly alert the immune system to potential threats without having to travel far.
“Lymph nodes serve as a resting place for T-cells, which are the immune system’s defense cells, remaining inactive until they are needed to combat infections or abnormal cells,” explained Natalie Livingston, Ph.D., who is the primary author of the study and currently a postdoctoral researcher.An archer at Massachusetts General Hospital discovered that cancers can deceive T-cells into remaining inactive, so an artificial lymph node was developed to help educate and activate T-cells when they are inserted alongside the lymph node. The researchers utilized hyaluronic acid, a hydrating substance commonly found in cosmetics and lotions, as well as in the body’s skin and joints, to create the artificial lymph node. Due to its characteristics, hyaluronic acid is frequently used in biodegradable materials, such as wound healing patches designed to be implanted or applied to the body. One of its properties is the ability to interact with T-cells through a ce.
In 2019, researchers from Johns Hopkins led by Jonathan Schneck, M.D., Ph.D., found that hyaluronic acid enhances T-cell activation on the cell surface.
For their latest study, the Johns Hopkins team used hyaluronic acid as the framework for their new lymph node, and incorporated MHC (major histocompatibility complex) or HLA (human histocompatibility antigen) molecules, which stimulate T-cells and other parts of the immune system. Additionally, they included molecules and antigens commonly found in cancer cells to educate T-cells on what to identify.
“By introducing various antibodies to the process, we were able to customize the immune response and redirect T-cells towards specific targets,” said the researchers.Livingston says that with the use of artificial lymph nodes, there is more control over the activation of T-cells. The artificial lymph node created is approximately 150 microns in size, which is twice the width of a human hair. This size allows it to stay under the skin and prevent it from being carried away in the bloodstream. Schneck, a professor at Johns Hopkins University, points out that this method requires fewer manufacturing steps compared to other cell-based therapies like CAR-T. Schneck holds positions in pathology, medicine, and oncology at Johns Hopkins University School of Medicine, and is the director of the Johns Hopkins Center for Translational Immunoengineering.As a member of the Institute for Cell Engineering, Kimmel Cancer Center and Institute for Nanobiotechnology. Current cell-based therapies involve removing T-cells from a patient, altering them outside of the body to recognize a specific type of cancer, and then reintroducing them into the patient. In our method, we inject T-cells along with an artificial lymph node, which primes and educates the T-cells inside the body. This allows the T-cells to travel anywhere to eliminate cancer cells,” said Schneck, who led the research team, along with Hai-Quan Mao, Ph.D., director of Johns Hopkins’ NanobiotechnoLivingston, Schneck and their team from the Johns Hopkins Oncology Institute conducted a study on mice that had been implanted with either melanoma or colon cancers to test the effectiveness of an artificial lymph node. The mice were injected with the artificial lymph node and T-cells six days after the tumors were implanted. The research team compared these mice with other groups that received different treatments, including artificial lymph node alone, T-cells alone (not activated by the artificial lymph node), and T-cells combined with a type of immunotherapy drug known as anti-PD-1. After nine days, the results of the study were analyzed for the mice with melanomas and colon cancers that were treated with a combination of an artificial lymph node, T-cells, and the anti-PD-1 drug showed the highest survival rates, with three out of seven mice still alive at 33 days, compared to other groups that lived only to about 26 days. Additionally, this group of mice experienced the slowest cancer growth rate, with their cancers taking between five and 10 days longer to double in size compared to the other groups.
The researchers also discovered that the artificial lymph node attracted a greater number of other immune cells and acted as an “immunologically active niche” to further stimulate the immune system. When T-cells were injected into the mice along with the artificial lymph node, there was a notable improvement in the mice’s survival rates and cancer growth rates.An increase in T-cell numbers up to nine times more plentiful was observed alongside the artificial lymph node, according to Livingston. The approach of the artificial lymph node differs from a cancer vaccine, which typically activates a dendritic cell to teach T-cells what to search for. Malfunctioning dendritic cells are common in people with cancer, and the artificial lymph node directly activates T-cells without the need for a dendritic cell. The research team intends to conduct further laboratory studies to incorporate additional immune signaling molecules into the lymph node and recruit more of the host’s immune cells to the artificial lymph node.environment.
“We utilized the knowledge from materials science and immunology to develop a potential therapy that creates its own community of immune cells — essentially a living drug,” explains Schneck.
The researchers have applied for a patent for the technology discussed in their study.
Funding for the study was supplied by the National Institutes of Health (R01EB029341, R21CA185819, P41EB028239, T32AI007417), the National Science Foundation, the Ruth L. Kirschstein Predoctoral Individual National Research Service Award (F31CA275271), the NIH Cancer Nanotechnology Training Center at the Johns Hopkins Institute for NanoBioTechnology.Technology, the National Science Foundation Graduate Research Fellowship, the ARCS Foundation, the Siebel Foundation, and the Natural Sciences and Engineering Research Council of Canada’s Postgraduate Scholarships — Doctoral Award. Other researchers from Johns Hopkins University who participated in the research include John Hickey, Hajin Sim, Sebastian Salathe, Joseph Choy, Jiayuan Kong, Aliyah Silver, Jessica Stelzel, Mary Omotoso, Shuyi Li, Worarat Chaisawangwong, Sayantika Roy, Emily Ariail, Mara Lanis, Pratibha Pradeep, Joan Glick Bieler, Savannah Est Witte, Elissa Leonard, Joshua Doloff, and Jamie Spangler.
