BioWorld International Correspondent

LONDON - Promising results from animal studies suggest that it soon may be possible to treat people with cancers of organs such as the breast, colon, skin and prostate so that any metastases from their primary tumors are killed.

The method, successfully used in a mouse model of cancer, relies on coating T cells isolated from the blood with a virus that preferentially kills tumor cells. On return to the body, the T cells are carried to the lymph nodes, where tumor cells often end up after detaching from the primary tumor. Because the nodes also house a huge population of immune cells, the destruction of the tumor cells within them also triggers a powerful immune reaction against the cancer.

Alan Melcher, a Cancer Research UK clinician scientist at the Leeds Clinical Centre, told BioWorld International: "We hope to begin clinical trials in humans using a similar method in about a year. In the long term, we would want to target cancers where we know that lymph node metastases are a very important danger sign, such as breast cancer and colorectal cancer."

Evidence to date suggested that viral therapies of that kind are nontoxic to humans, he added. "People would still have their standard therapy, such as surgery, chemotherapy and radiotherapy, but we could follow that with viral therapy to target lymph node metastases, without adding any additional morbidity to patient treatment," Melcher said.

A report of the study by Melcher and his colleagues appeared in the Jan. 8, 2008, issue of Nature Medicine, in a paper titled: "Purging metastases in lymphoid organs using a combination of antigen-nonspecific adoptive T cell therapy, oncolytic virotherapy and immunotherapy." The method has been developed as the result of an international collaboration between scientists based at Cancer Research UK's Clinical Centre in Leeds and colleagues at the Mayo Clinic in Rochester, Minnesota.

Writing in Nature Medicine, the team concluded: "[This method] is technically simple, and it has the potential to be used clinically for a wide variety of common cancers in which the greatest risk to the patient stems from lymph node-disseminating metastatic cells."

In many types of cancer, including those of the breast, colon, prostate, head and neck and skin, the greatest threat to the health of the individual is not from the primary tumor but from secondary tumors, which spread by seeding cancer cells to other parts of the body.

Any tumor cells that detach from the primary tumor will pass through a lymph node, so any treatment that can kill tumor cells within the lymph node would be very useful, as it would limit the spread of the cancer.

Melcher's team decided to build on the observation that naïve T cells (those which have not yet encountered an antigen) naturally migrate from the peripheral blood to the lymph nodes. They hypothesized that they could isolate populations of ordinary untargeted T cells from the blood, and use those to carry viral vectors to the lymph nodes, where the viruses could kill the tumor cells.

They used vesicular stomatitis virus (VSV), a virus found in horses and cattle, as their therapeutic agent. That virus preferentially kills cancer cells, while normal cells are able to survive. In addition, the death of the tumor cells in the lymph nodes primes nearby T cells to recognize cancer antigens.

"This antitumor immune response is key," Melcher said, "because it should operate throughout the body, killing cancer cells wherever they are."

Using a mouse model of lymph node metastases from an established primary tumor, the researchers showed that 10 to 14 days after the transfer of T cells coated with VSV the animals' draining lymph node and spleens were consistently free of tumor cells.

The researchers also were able to show that mice treated with a single dose of lymphocytes carrying VSV developed potent T cell responses to the tumor used for the model.

Colleagues at the Mayo Clinic now are working on developing a type of VSV that can be used in clinical trials in humans. Melcher and his colleagues also plan to investigate use of other viruses that can be used to kill cancer cells in humans, such as reovirus.