Vaccine would tap tumors' RNA

Zürich, Switzerland - A project under way at Erlangen University will test the ability of RNA taken from patients' own tumors to train their immune systems to attack skin cancer cells.

Stumbling block Tumor recognition has long been a stumbling block for cancer vaccine research.

Researchers aim to develop efficient killer T-cells with a very high affinity for tumor cells. At press time, the Erlangen team was planning to begin its trial in late September. In the meantime, they continue working to refine their technique and to establish whether they can reliably generate melanoma RNA in a laboratory and introduce it to dendritic cells (DCs).

"So far, we are quite happy with our progress," he tells Dermatology Times.

In principle, researchers working with Dr. Eli Gilboa at Duke University already have succeeded in using this approach to address renal cancer (Su et al. Cancer Res. May 2003. 1;63(9):2127-2133).

Although interest in immune-sys-tem surveillance of cancer dates back to the 1960s, early strategies succeeded only through chemically induced cancer antigens.

"It was just then understood that the immune system has a tolerance against many antigens," according to Dr.Kaempgen. "By inducing cancer antigens through chemical means, you're introducing truly new antigens. So you don't have that tolerance, and you really get immune responses. The question is, how can we move this into the clinic?"

Answer lies in DCs Many researchers believe the answer lies in DCs, which are highly active antigen presenters.

"The limitation there is, what kind of antigen are you showing to the immune system?" Dr. Kaempgen asks. "Differentiation and cancer testis antigens have all been seen by the immune system. So the really active T-cells are either deleted or checked by regulatory cells. We believe that by using RNA, we might be able to present some new antigens to the immune system that are tumor- and patient-specific, so you get those high-affinity T-cells activated," he says.

Another issue that has perplexed cancer-vaccine researchers is determining what costimulatory signals must be presented to elicit immune responses.

"Most people think about IL-12 and look at the DC in vitro," Dr. Kaempgen says. "If it is a high IL-12 producer, it's assumed you have a good vaccine. If it's a low IL-12 producer, then you don't. But this does not seem to be true. So you do not need a DC that produces high amounts of IL-12 in vitro, but a DC that produces some sufficient amount of IL-12 in vivo, at the right place and at the right time."

Other stumbling blocks Other stumbling blocks include ensu-ring that injected DCs migrate into lymph nodes and determining how many DCs are needed to elicit an immune response.