Bacteria take new role as cancer vaccine.

Oral vaccines are becoming commonplace: Immunity to typhoid and cholera, for example, now comes without a needle prick, and other such vaccines await testing. But vaccines for cancer, let alone oral ones, seem years distant.

Recent work with mice, however, makes the idea of such vaccines a little less fantastic. In the Nov. 1 Cancer Research, scientists at the University of Pennsylvania in Philadelphia and the Johns Hopkins Medical Institutions in Baltimore report success with an oral vaccine against two types of specially tagged tumors.

The vaccine itself, as novel as that result, consisted of a live, genetically engineered version of a bacterium, Listeria monocytogenes, usually found as a food contaminant. Fed to mice, these modified bacteria induced a powerful immune reaction.

"We've based our vaccine on its ability to induce immune cells to destroy tumors, just as they'd kill viruses, for example," says Pennsylvania's Yvonne Paterson. The immune cells in question-cytotoxic T lymphocytes, or CTLs-recognize foreign proteins on diseased or infected cells. Engineering that recognition became the idea behind the vaccine development.

The researchers first transferred a nonmouse gene called NP into laboratory-grown cells from renal or colon cancers in mice. The gene directed the cancer cells to make a protein, also called NP. These NP-marked cells readily grew into tumors when the scientists implanted them in the mice.

Meanwhile, the researchers inserted the NP gene into Listeria and fed the bacteria to tumor-carrying mice. The Listeria churned out NP protein, and the mice responded by producing CTLs that homed in on NP.

Attacked by the CTLs, the bacteria lasted less than 6 days-a typical fate when immune response is strong. But the tumors also had a bad time: Because the cancer cells carried the NP protein, the CTLs recognized and attacked them too. The vaccine cleared all tumors from 60 percent of the mice with renal cancer and 50 percent of those with colon cancer.

"It's kind of wild to think you could make cancer go away with something you swallow," says Paterson, "but a benefit could come not only from treating the cancer, but from being far less invasive."

Now the researchers plan to move on to human cancers. The team has inserted into mouse tumors a gene taken from the human papilloma virus (hpv), which causes 90 percent of human cervical cancers. The group hopes to attack these mouse tumors by stimulating CTLs that recognize the hpv protein.