University Of Michigan Vaccine Triggers Immune System

August 04, 1998

ANN ARBOR---Using a vaccine made from specialized white blood cells called dendritic cells spiked with cancer proteins, University of Michigan scientists have found a way to activate the immune system to attack malignant tumors and prevent the development of new tumors in mice.

Immunization with the dendritic cell vaccine was effective against two types of solid tumors---sarcomas and breast carcinomas---in two unrelated strains of mice," said James J. Mulè, professor of surgery in the U-M Medical School and director of the Tumor Immunotherapy Program in the U-M Health System's Comprehensive Cancer Center. "Based on these encouraging results, we have begun a Phase I clinical trial in pediatric and adult patients with advanced solid tumors."

Results of the study were published in the Aug. 4 issue of the Proceedings of the National Academy of Sciences. Ryan C. Fields, from Bloomfield Hills, Mich., who received his U-M undergraduate degree in May 1998, and Koichi Shimizu, M.D., U-M research fellow, are joint first authors on the study.

Fields, Shimizu and Mulè used immature dendritic cells from mouse bone marrow as the basis for their vaccine. Dendritic cells are specialized white blood cells whose job it is to alert the immune system to the presence of invading cancers, bacteria or viruses, so the invaders can be surrounded and destroyed. When they find cancer cells, dendritic cells sound the alert by displaying pieces of tumor proteins called antigens on long projections extending from the center of the dendritic cell.

Like Cinderella's prince searching for a woman who matches the glass slipper, the dendritic cell presents these antigens to other white blood cells called T-lymphocytes until it finds those with receptors that fit the tumor antigen. Once a match is made, T-lymphocytes produce messenger chemicals which stimulate production of a flood of T-lymphocyte "clones," all equipped with the exact receptor needed to attack and destroy one specific type of tumor cell.

"Cancer cells often hide from lymphocytes by becoming invisible," Fields explained. "Instead of displaying foreign proteins on the surface of tumor cells, most remain inside the cell where the immune system cannot detect them. Dendritic cells bring these hidden antigens out of hiding triggering this intense immune system response."

While other researchers are experimenting with tumor vaccines made from single tumor peptides mixed with dendritic cells, Mulè and his colleagues were the first to use whole tumors called lysates---tumor cells which have been frozen and thawed several times to kill them. "By using the entire tumor cell, we are sensitizing the immune system to attack all the antigens in that tumor, rather than just one or two," said Mulè. "A broader immune response makes it less likely that tumor cells will escape detection."

Significant results from the U-M study include:

U-M scientists use immature dendritic cells fresh from the bone marrow's production factory, rather than mature dendritic cells which have already circulated through the lymphatic system to other organs. "At this early undifferentiated stage of development, it is easier to sensitize them to react to an individual's specific cancer antigens," Mulè explained.

The research was supported by the National Cancer Institute/National Institutes of Health, the U.S. Army Research Office and by gifts from C.J. and E.C. Aschauer and Abbott Laboratories to the U-M's Department of Surgery and the Tumor Immunotherapy Program.

EDITORS: A black-and-white photomicrograph showing a dendritic cell, tumor lysates and T-lymphocytes is available upon request.

University of Michigan

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 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