Dissecting Cancer Vaccines

MONTREAL, CANADA--If there's one thing cancer vaccine developers would like to know, it's why only a handful of patients respond strongly to their inventions. Now at an immunology meeting here, a team of scientists reported that a set of patients with metastatic melanoma may be revealing an answer to that mysterious question.

Cancer vaccines involve using a patient's immune cells to set off an attack against his or her cancer. Although results from cancer vaccine trials have often been disappointing, there's continued interest because the strategy makes so much sense in theory. Doctors have had the most success with vaccines to treat melanoma, a skin cancer that's often deadly if it spreads.

Immunologist Nathan Martinez of the Queensland Institute of Medical Research in Australia and his colleagues are testing a vaccine made from patients' dendritic cells, a type of white blood cell that typically triggers an immune response against pathogens. Researchers create a personalized vaccine for each patient by harvesting and concentrating immune cells. At the annual Federation of Clinical Immunology Societies and the annual International Union of Immunological Societies, Martinez reported that of 43 patients with advanced melanoma who are receiving vaccinations, seven have responded completely, their tumors shrinking to undetectable levels. That low response rate is par for the course when it comes to cancer vaccine. So, Martinez's team decided to examine whether those seven fortunate patients shared anything in common.

When they analyzed patient blood samples taken before the vaccinations, the researchers found that the patients who responded had lower levels of a protein, S100B, compared with those who didn't. S100B is normally held inside cells, but some scientists believe that when tumors grow, healthy cells begin dying and release the protein. Martinez speculates that increased levels of S100B signal a large tumor burden--something that can be tough to measure, and that may make one less likely to respond to a vaccine. Just as interesting was another finding: In all of the responders tested so far, four out of seven, cytotoxic T cells from pre-vaccine blood samples could kill cells from that patient's tumor in a petri dish. This was not the case for patients who hadn't been helped by the vaccine.

"I've never seen such a striking correlation," says Lloyd Stoolman, an immunologist at the University of Michigan, Ann Arbor. Although he's skeptical about the long-term use of dendritic cell vaccines, which he thinks may be less effective than other types, he agrees that the ability to predict success in cancer vaccine trials is the "holy grail" of the field.

Related sites
Background on cancer vaccines from the National Cancer Institute
Cancer immunotherapy at the Queensland Institute of Medical Research