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March 2002
Vol. 5, No. 3, p 17.
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Tumor vaccine assembly, in situ

Prophylactic efficiency
Prophylactic efficiency. Growth of a Lewis lung carcinoma 3LL tumor inoculated with a two-polymer-rod (MIP-3β and tumor-associated antigen) vaccine system (red curve), compared with control implantations and no implantation (remaining curves). (Adapted from Nat. Biotechnol. 2002, 20, 64–69.)
Studies have shown that laboratory animals can exhibit a potent antitumor immune response when they are administered a vaccine composed of dendritic cells (DCs) and tumor-associated antigens (see “Tailor-made cancer vaccines”, Modern Drug Discovery, Oct 2001, p 11). Currently, the production of such vaccines requires multiple manipulations of DCs outside the body to make the cells mature, and then fusing them to customized antigens. This process renders the vaccines too costly and time-consuming to be practical.

Enter researchers at the University of Texas (UT) Southwestern Medical Center at Dallas. They recently reported the creation of an artificial trap that captures and customizes DCs right under the skin (Nat. Biotechnol. 2002, 20, 64–69). This new process shortens the time span of the process from 10 days to just 24 hours.

DCs are specialized white blood cells that signal T lymphocytes to multiply and initiate an immune response. The epidermis contains immature DCs known as Langerhans cells, which mature and migrate to draining lymph nodes upon interaction with a hapten molecule. Chemokines attract the migrating cells and help mediate the process.

The researchers created a trap for Langerhans cells beneath the epidermis in mice by implanting an ethylene–vinyl acetate polymer rod incorporated with a chemokine known as MIP-3β. After the rod was implanted, it released MIP-3β into the body, and the researchers applied a hapten to trigger migration of the Langerhans cells. The rod temporarily entrapped the cells, which eventually homed to the lymph nodes.

In a second experiment, a polymer rod releasing tumor-associated antigens was implanted along with the chemokine-containing rod. “We thought these Langerhans cells would carry the tumor-associated antigen to the draining lymph nodes and initiate protective immunity against tumor development,” said Akira Takashima, professor of dermatology at UT Southwestern and coauthor of the study, in a statement released by UT Southwestern. Experiments with several tumor models in mice demonstrated that this strategy was effective, in many cases almost completely preventing the development of inoculated tumors.

By creating an in vivo process, this method could bring antitumor vaccines one step closer to reality.

CHRISTEN L. BROWNLEE

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