Quest for vaccine continues

May 1, 2007

Researchers are honing in on what might make melanoma vaccines work, but the immune response is complex, dynamic and, so far, no vaccine has found its way to a successful large-scale trial. That's not stopping scientists from trying to ferret out and put to use the mechanisms of vaccine efficacy, however.

Key Points

The principal area in which melanoma vaccines show promise, according to Jean Claude Bystryn, M.D., professor of dermatology, New York University School of Medicine, New York, is in effectively increasing immune reactivity against melanoma and appearing to slow cancer's progression.

While the approaches to developing the vaccines vary, all vaccines aim to rev up the immune system so it can react more vigorously and effectively kill or hold at bay melanoma cells.

"There are two key ingredients involved in making the vaccines," Dr. Bystryn says.

"One is that the vaccine must have certain antigens" that will trigger antitumor responses, he tells Dermatology Times.

The challenge is that researchers know a lot about different antigens present in melanoma, but they do not have a good grasp of which antigens can induce this type of response.

The other ingredient and corresponding challenge is that antigens that can trigger effective immune response have to be present on the tumor being treated. The problem: Antigens expressed by different melanomas in different people will vary.

"In fact, the antigens expressed by different melanoma cells - even in the same person or even within the same tumor nodule - also vary," Dr. Bystryn says.

Identifying the right antigens

Scientists construct cancer vaccines in various ways. But they all tend to use two broad strategies, according to Dr. Bystryn.

One involves preparing a composition of antigens they think will be effective, and the other broad set of strategies looks at how they can rev up the ability of these antigens to stimulate immune responses in cancer.

To come up with an appropriate composition of antigens for a vaccine, researchers might use any of three basic strategies.

"The downside of this approach is that about 99 percent of what ends up in the vaccine is unrelated to what you need," he says.

At the end of the day, however, there is no perfect way to identify the spectrum of antigens one would need for an effective melanoma vaccine.

Revving immune response

Vaccines are made up of two components: the antigen that triggers the immune response and the adjuvant that makes the response stronger.

There are various ways to use adjuvants to rev the immune response. Two popular approaches include the use of dendritic cells and immunomodulatory molecules.