In an experiment using laboratory mice, Dr. Silvia Formenti, head of the New York University department of radiation oncology, and colleagues found that combining the drug bortezomib and radiation stimulated the immune system to shrink the main tumor and attack secondary cancers not directly targeted by the treatment.

Bortezomib, also known as PS-341, is a proteasome inhibitor being developed by Millennium Pharmaceuticals under the brand name Velcad. It has been granted fast-track status by the US Food and Drug Administration (news - web sites) for treating multiple myeloma.

"The combination of ionizing radiation and PS-341 can elicit anti-tumor mechanisms capable of controlling tumor growth at a remote site. This finding is extremely important as it suggests that it may be possible to use this combination regimen to treat cancer patients and at the same time vaccinate them against their tumor," the researchers said at the EORTC-NCI-AACR cancer conference here.

Cancers are able to grow without being rejected by the body because they somehow induce "tolerance" and slip past the immune system unnoticed, Formenti explains.

"The big question is, which manipulations do we have to upset this tolerance?"

Sandra Demaria, a basic scientist involved in the work, hypothesized that tumor cell death induced by chemotherapy and radiation together "has some special ingredient that elicits an immune response," Formenti said.

Evidence from other research suggested what might be needed to promote an immune response in tumors is activation of dendritic cells, which alert the immune system to the presence of unwanted material by carrying small pieces of tumor cells, known as antigens, on their surface.

"The hypothesis is that if you give chemotherapy and radiation you induce a lot of sudden cell death and instead of this release of antigens being ignored, they will be more likely to be picked up with dendritic cells."

The researchers injected breast cancer (news - web sites) cells under the skin of mice at two places--100,000 cells in one site to create a "primary" tumor and half as many in another place to form the "secondary" tumor.

They used bortezomib because it triggers the release of heat shock proteins, which also stimulate immunity, Formenti said.

"When you give PS-341 and radiation together of course they have an additive effect, so they get more growth delay in the radiated tumor. Then, what is interesting, and provocative is that they get it on the other one and it is more than the PS-341 alone," the researcher said.

"The second tumor didn't get radiation but it behaves as if it did."

The results of the study have prompted Formenti's group to start a clinical trial in women with advanced breast cancer.

They are asking women to take part in the study when they reach a plateau of response to normal chemotherapy. The researchers then target radiotherapy on a secondary cancer, and at the same time boost the number of dendritic cells by giving the women a drug called GM-CSF.

At the moment, "it is a long-shot," Formenti said. "But if this dream were to come true it will have huge implications.

"Instead of expecting to cure patients of cancer by killing down to the last cancer cell, we're saying kill some cells and potentiate the patient's immunity to pick up those antigens and self-vaccinate them against their tumor."