A new type of cancer vaccine tested in mice appears to overcome some of the major hurdles associated with the treatment approach, according to a paper published today (November 25) in Science Translational Medicine.

The technology, which the researchers have already licensed to a biotechnology company, is being developed for clinical trials of melanoma.

Immune cells are attracted by chemicals released by the polymer matrix (shown here) to sample the tumor molecules embedded within. Image: Edward Doherty, Omar Ali and MicroVision Labs Inc.

The "reliable and careful" experiments shed light on a "promising approach" for a vaccine-based treatment for cancer, said Eli Gilboa a cancer immunologist from the University of Miami, who was not involved in the work. "It's a simple paper," he said, "in a good way."

The new technology consists of a small sponge, the diameter of a pencil eraser, embedded with a vaccine and inserted under the skin of mice with melanoma. The researchers saw an activation of the immune cells that attack tumors, as well as a suppression of regulatory T cells (Tregs), often recruited by the cancer to suppress the immune reaction. "In this particular model," Gilboa said, "the [immune response] is unprecedented."

Trying to force the immune system to fight cancer has been a tantalizing, though frustrating project for immunologists. Although the immune system can fight the very early stages of cancer (described in this month's issue), it is not generally effective at fighting the advanced stages of cancer. Larger tumors, which have accrued multiple mutations, can escape immune detection in various ways, and also suppress the immune reaction.

In this study, David Mooney at Harvard and his colleagues coated a polymer sponge with three vaccine components, including a puree made from their mouse model's melanoma cells and a cytokine known to attract two types of dendritic cells to the area. Dendritic cells direct the immune reaction by presenting cancer peptides to immune cells, priming them against the cancer. But dendritic cells can also trigger immune suppression, so the researchers embedded small lengths of nucleic acid that mimic bacterial DNA throughout the polymer matrix. With the bacteria-like nucleotides "you make the immune cells think they have a bacterial infection," which creates a robust immune responses involving many immune cell types, Mooney said. The strength of the reaction is likely to prevent immune suppression.

"I think the reason people are excited" about the research, said Mooney, "is that it has all of the molecular and cellular signatures of a strong vaccine reaction."

The approach would necessitate biopsies from each individual cancer patient to coat the polymer matrix, requiring a personalized approach. Mooney said he plans to try the approach using tumor antigens that are common to multiple tumors to see if they can develop a more generic vaccine.

Mooney will also explore some of the basic biology behind the process. "The results are very dramatic," said Mooney, but "mechanistically we don't understand a lot of what's happening" inside the polymer. The technology is already being developed for human clinical trials of melanoma by a company called InCytu. In the meantime, Mooney plans to explore the technology for other cancer types as well as looking into whether this approach might improve vaccines for infectious diseases.


Related stories:

Immune system vs. Cancer
[November 2009]

A complement for cancer?
[29 September 2008]

The ecology of tumors
[April 2006]