UT Southwestern researchers develop new method of delivering vaccines

December 28, 2001

DALLAS - Dec. 28, 2001 - Researchers at UT Southwestern Medical Center at Dallas have developed a quicker, more cost-efficient method of delivering dendritic cell-based vaccines - a discovery that moves anti-tumor vaccines closer to a practical reality.

Until now, the conventional method to develop these vaccines involved extracting dendritic cells, which initiate immune responses to bacteria, viruses and cancer cells, from the body, then culturing and expanding the cells in a petri dish, loading them with tumor-associated antigens - substances the immune system recognize on cancer cells - and finally administering them through a vaccine.

Dr. Akira Takashima, professor of dermatology at UT Southwestern, reported in today's Nature Biotechnology that this expensive and time-consuming process has prevented broader clinical applications for dendritic cell-based vaccines.

In the UT Southwestern study, Takashima developed and tested a new procedure in mice that enabled researchers to manipulate dendritic cells in the skin rather than in a petri dish. This new process streamlines the conventional method from 10 days to 24 hours.

Dendritic cells are specialized white blood cells that signal T lymphocytes, critical components of the immune system, to multiply and initiate an immune response. The epidermis, or outermost layer of normal skin, contains immature dendritic cells known as Langherhans cells.

Upon exposure to a topical chemical called a hapten, Langerhans cells mature and migrate from the epidermis to draining lymph nodes. Small molecules called chemokines attract the trafficking cells and help mediate this process.

"Lymphatic endothelial cells produce a chemokine known as MIP-3ß, which binds to a corresponding receptor called CCR7. Langerhans cells utilize CCR7 to migrate from the epidermis to draining lymph nodes," said Takashima. "We incorporated this chemokine into a polymer rod so that it could be released in a controlled fashion."

The researchers created an artificial trap for Langerhans cells by implanting under the skin a polymer rod synthesized with ethylene-vinyl-acetate to release MIP-3ß. After the rod was implanted, researchers applied hapten to trigger Langerhans-cell migration. The rod temporarily entrapped the Langerhans cells, which eventually homed to the lymph nodes. The procedure resulted in accumulation of Langerhans cells around the rod, Takashima said.

In a second experiment, a polymer rod releasing a tumor-associated antigen was then implanted under the skin.

"We thought these Langerhans cells would carry the tumor-associated antigen to the draining lymph nodes and initiate protective immunity against tumor development. Our subsequent experiments with several tumor models have, indeed, demonstrated the preclinical efficacy of this strategy. We believe that our in situ Langerhans-cell vaccine format represents a breakthrough in the tumor vaccines field, thus moving it toward practical medicine," said Takashima.
Dr. Tadashi Kumamoto, postdoctoral researcher in dermatology at UT Southwestern, was also involved in the study, which was supported by grants from the National Institutes of Health.

To automatically receive news releases from UT Southwestern via e-mail, send a message to UTSWNEWS-REQUEST@listserv.swmed.edu. Leave the subject line blank and in the text box, type SUB UTSWNEWS.

UT Southwestern Medical Center

Related Immune System Articles from Brightsurf:

How the immune system remembers viruses
For a person to acquire immunity to a disease, T cells must develop into memory cells after contact with the pathogen.

How does the immune system develop in the first days of life?
Researchers highlight the anti-inflammatory response taking place after birth and designed to shield the newborn from infection.

Memory training for the immune system
The immune system will memorize the pathogen after an infection and can therefore react promptly after reinfection with the same pathogen.

Immune system may have another job -- combatting depression
An inflammatory autoimmune response within the central nervous system similar to one linked to neurodegenerative diseases such as multiple sclerosis (MS) has also been found in the spinal fluid of healthy people, according to a new Yale-led study comparing immune system cells in the spinal fluid of MS patients and healthy subjects.

COVID-19: Immune system derails
Contrary to what has been generally assumed so far, a severe course of COVID-19 does not solely result in a strong immune reaction - rather, the immune response is caught in a continuous loop of activation and inhibition.

Immune cell steroids help tumours suppress the immune system, offering new drug targets
Tumours found to evade the immune system by telling immune cells to produce immunosuppressive steroids.

Immune system -- Knocked off balance
Instead of protecting us, the immune system can sometimes go awry, as in the case of autoimmune diseases and allergies.

Too much salt weakens the immune system
A high-salt diet is not only bad for one's blood pressure, but also for the immune system.

Parkinson's and the immune system
Mutations in the Parkin gene are a common cause of hereditary forms of Parkinson's disease.

How an immune system regulator shifts the balance of immune cells
Researchers have provided new insight on the role of cyclic AMP (cAMP) in regulating the immune response.

Read More: Immune System News and Immune System Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.