Dendritic Cell Melanoma Vaccine

For this article, Eugene Russo interviewed Frank O. Nestle, a researcher in the department of dermatology at the University of Zurich Hospital. Data from the Web of Science (ISI, Philadelphia) show that this paper has been cited significantly more often than the average paper of the same type and age. F.O. Nestle, S. Alijagic, M. Gilliet, Y.S. Sun, S. Grabbe, R. Dummer, G. Burg, D. Schadendorf, "Vaccination of melanoma patients with peptide- or tumor lysate-pulsed dendritic cells," Nature Medicine, 4:328-32, March 1998. (Cited in more than 220 papers since publication) Known to be an immunogenic cancer, melanoma has been increasingly targeted with a variety of immunotherapies in the past few years. Scientists know that some tumor-specific cytotoxic T cells recognize certain antigens on melanoma tumors, making a properly crafted and triggered immune response a potentially excellent way to rid the body of the disease. This paper reported the first-ever melanoma human clinical immunotherapy trial to use skilled antigen-presenting cells called dendritic cells. Researchers took existing melanoma antigens, isolated dendritic cells from the blood of patients, pulsed those cells with the antigens, and injected them into the patient--specifically, into the lymph node, the site of humoral and cell-mediated immune reactions. Several of the 16 patients tested had positive results. Investigators got an immune response against the antigens in most of the patients and a positive clinical response in several of them. Side effects of the treatment were few--only a transient fever or a purely cosmetic skin disorder called vitiligo, in which sufferers lose pigment in patches of skin. Most of the responders are still alive today. "That means that we are not only able to induce an immune response and to induce a regression of the tumor in the absence of severe side effects, but that we can also induce a long-lasting antitumor response," explains lead author Frank O. Nestle. Patients continue to get regular vaccinations. Frank O. Nestle Nestle contends that right now dendritic cell vaccinations are probably the most popular melanoma immunotherapy. He points out, however, that the tricky isolation and expansion of the cells still make it very cumbersome. Injecting a single peptide into the skin as described in the article below would be much easier. If dendritic cell therapies are proven the most effective, says Nestle, in future trials researchers might inject peptides specifically targeting skin dendritic cells to coax the mixture into the lymph node and activate T cells. It may also be possible in the future to target antigens to dendritic cells in vivo by, for example, administering a growth factor cocktail before injecting the antigen. Since this paper and the one below appeared, melanoma treatments have become the cutting edge of cancer immunotherapies worldwide. On Feb. 11-12, the University of Zurich Hospital hosted an international meeting and workshop on clinical trials in dendritic cells (www-usz.unizh.ch/dcm/index.htm) sponsored by the International Union Against Cancer. Investigators continue to play with the dozens of therapy permutations based on mode of delivery and method of increased potency. "There are 50 or 100 ways to make the cells and at least four different ways to inject them," says Nestle. Methods of delivery include intranodal, as in this paper, as well as intravenous, subcutaneous, and intradermal. Nestle's top future priority will be to target not only cytotoxic T cells by choosing class I antigens, but also helper T cells by choosing major histocompatibility complex (MHC) class II antigens. Nestle continues to be encouraged by current studies based on the results of his 1998 paper. "To me, the most interesting point looking back at the paper is that most patients which we have treated [and] which responded are still responders," he says. "And the other important thing is that up till now ... we haven't seen any serious side effects."

Dendritic Cell Melanoma Vaccine

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