A Better Way to Deliver Dendritic Cell Vaccines

Conducted by scientists at the University of Texas Southwestern Medical Center (UT, Dallas, USA), the study was published in the December 28, 2002, issue of Nature Biotechnology.

Dendritic cells signal T lymphocytes to multiply and initiate an immune response against bacteria, viruses, and cancer cells and are thus good vaccine candidates. However, the conventional method of culturing cells in a petri dish is a time-consuming, expensive process that has deterred broad vaccine application. Now, a new procedure developed and tested in mice enables researchers to manipulate dendritic cells in the skin instead of a petri dish and reduces the time required from 10 days to 24 hours.

Here is how the new delivery method works. Upon exposure to the chemical hapten, immature dendritic cells in the epidermis known as Langerhans cells mature and migrate to draining lymph nodes. A key chemokine (MIP3beta) helps to attract the migrating cells and mediate the migration process. The researchers created an artificial trap for Langerhans cells by implanting a polymer rod under the skin that was synthesized with ethylene-vinyl-acetate to release this chemokine. After the rod was implanted, hapten was applied to trigger the Langerhans cell migration. The cells homed in to the lymph nodes and created an accumulation of Langerhans cells around the rod.

In a second experiment, the researchers utilized a polymer rod releasing a tumor-associated antigen that was implanted under the skin, believing that the Langerhans cells would carry the antigen to the draining lymph nodes and initiate immunity against tumor development. Subsequent experiments with different tumor models have demonstrated that this strategy is efficacious.

"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 Dr. Akira Takashima, professor of dermatology at UT Southwestern.




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University of Texas Southwestern Medical Center