Melanoma vaccines show promise

Dr. Rudolph presented, "Melanoma Vaccines - A Review of Current Clinical Trials" at the 63rd Annual Meeting of the American Academy of Dermatology (AAD) here.

"Both a forthcoming article Dr. Jean-Claude Bystryn and I have written and the data we presented at the AAD discuss the use of vaccines in the treatment of advanced cancers," Dr. Rudolph says. "We reviewed data from the NIH clinical trials database and the International Drug Database ( http://IDDB.com/), a subscription-based industry publication. This data was then used to generate a representative list of all current clinical trials. It is not all-inclusive, but rather focuses on the major phase 2 and (phase) 3 melanoma vaccine trials currently under way or recently completed," Dr. Rudolph says.

"In general, when someone talks about a melanoma vaccine, most people picture an injection you might give a healthy patient, similar to the influenza vaccine, which would prevent the future development of a melanoma," Dr. Rudolph explains. "What these cancer vaccines actually are is something quite different. They are a selective approach to treat advanced cancers which already exist, and they are intended to stimulate the patient's own immune system to attack and destroy these cancer cells. As such, melanoma and other cancer vaccines are quite different from what we once thought vaccines to be."

What's in a vaccine?Two components comprise all cancer vaccines: 1) tumor antigen(s), whose purpose it is to stimulate an immune response against the cancer and 2) an adjuvant, whose purpose is to increase the strength of these responses. Adjuvants are necessary, as the immune response induced by tumor antigens alone are quite weak.

"In the information we presented at the February 2005 AAD meeting, we backed up a bit and first discussed some of the challenges in designing an effective vaccine," Dr. Rudolph explains. "We discussed what strategies are used to construct cancer vaccines and what components go into their manufacture. We broke melanoma vaccines into non-purified/cellular, semi-pure and pure/defined groups. We went through the information we had collected and separated all trials into these three categories, and we compiled a list of the antigens used in each vaccine. We also discussed what types of adjuvants are being used, as they are quite critical in the efficacy of these vaccines."

Investigations A large number of different adjuvants are being investigated. These range from modifications of the physical or biochemical properties of melanoma cell antigens to classical adjuvants and immunomodulators.

"There are a number of different adjuvants currently in use, some of which have been used for quite some time and others, which are quite new," Dr. Rudolph says. "Some of them include patented adjuvants, like Detox, which Corixa has as a component in their Melacine vaccine."

Another vaccine developed in Dr. Bystryn's lab uses IL-2 in liposomes. Some other adjuvants include GMCSF and pulsed dendritic cells, according to Dr. Rudolph.

Still on the horizon Dr. Rudolph discussed four completed, randomized controlled melanoma vaccine trials and the impact of their results on the further development of vaccines.