ABSTRACT
This chapter considers an approach to vaccination that is being tested in the setting of malignant melanoma. The method constitutes actively immunizing cancer patients with a sample of their own dendritic cells (DCs) charged with melanoma antigens (MelAgs). The latter can range from previously defined melanoma peptides to a broad group of MelAgs delivered with melanoma cells or RNA derived from there. This active immunization approach is very different from standard approaches of injecting vaccine antigens intramuscularly or intracutaneously, and, clearly, cell therapy is useful only in select contexts. Nevertheless, research on DCs in cancer therapy could be broadly instructive. First, the approach provides a means to load DCs with many tumor antigens, which may be vital in eliciting protective immunity to human cancers. Second, the use of ex vivo-derived, antigen-loaded DCs provides an opportunity to monitor and to manipulate several aspects of DC physiology that are pertinent to the control of immune responses. Third, DC therapy represents a nontoxic means to study the immune response to human cancers in patients who often do not have alternative therapies, as in stage IV melanoma. At this stage, it is not established if active immune cells, once generated by active immunization with DCs, will bring about tumor regression and prolong survival in patients, but some preliminary Phase I studies are encouraging, as summarized briefly below.
