Seattle, WA--Scientists at the Pacific Northwest Research Institute (PNRI, now PNDRI) in Seattle announced today the development of a promising new cancer vaccine technology. Their report points the way toward cancer vaccines that will trigger rejection of tumors by the immune system.

In the April 6 issue of Proceedings of the National Academy of Sciences (PNAS), the researchers describe a process whereby cells from melanoma, a highly malignant skin cancer, are engineered to express a particular molecule that induces the immune system to attack and kill them. Various forms of cancer survive and flourish because they are able to evade immune detection. The study reported in this publication is part of a program PNRI researchers are conducting to devise new ways to make cancer cells more conspicuous, and thus more vulnerable to immune rejection.

"We're looking for the best ways to develop tumor vaccines for therapy of cancer," says Karl Erik Hellstrom, the lead researcher in the PNAS study. "The importance of this paper is that it moves us closer to the kind of vaccine we can use to treat human cancers clinically."

The molecule the Hellstrom group studied, CD83, is expressed on dendritic cells which play a key role in the immune system by presenting antigens to certain cells (T lymphocytes) which can find and reject tumors that express them. Two previous publications from PNRI by Drs Nathalie Scholler, Jeffrey and Martha Ledbetter and Ingegerd and Karl Erik Hellstrom had shown that an interaction between CD83 and its ligands, which in man are primarily expressed on monocytes, plays an important immunoregulatory role. In the study now being published, the Hellstrom group altered melanoma cells from mice so that they expressed CD83. When injected back into the mice, the modified melanoma cells attracted lymphoid cells that expressed the CD83 ligand and that led to a strong immune response to the injected cells.

"But this method caused more than the destruction of the artificially engineered cells," according to Hellstrom. "It also immunized against melanoma cells that had not been modified to express CD83". Therefore the researchers believe that they can educate the immune system to attack a whole host of tumor cells sharing the same antigens by triggering its response to some cells that have been specifically engineered for use as a vaccine.

This general approach has also successfully employed other immunostimulatory molecules that can be expressed on tumor cells. In an earlier publication with the Ledbetters and others, the Hellstroms showed that a different immunostimulatory molecule transfected into tumors can trigger an effective immune response. The publication now coming out in PNAS goes on to demonstrate that the two immunostimulatory molecules can be used together to create even stronger immunization so as to destroy tumor cells that are not killed by either type of vaccine used alone.

"Melanoma--especially when it has metastasized," Hellstrom says, "is a major unmet medical need. Most patients with this condition die. What we're working to develop is a therapeutic vaccine or combination of vaccines by which the immune system can be employed to destroy tumor cells that sometimes remain after treatment for a primary melanoma or after detectable metastases have been removed." The next step will be to put CD83 into human melanomas to demonstrate that this vaccine approach can work effectively for human cancers. Work is also being started to develop vaccines in which genes are combined that encode melanoma antigens together with CD83. Although Karl Erik and his wife and long-term collaborator Ingegerd Hellstrom focus this work on melanomas, they believe that a similar approach can be taken for other cancers as well.