Review: dendritic cell immunotherapy for melanoma.

Abstract

Melanoma is a particularly aggressive malignant tumour of the skin that is influenced by genetic, environmental and physiological elements. Since current therapy for melanoma is limited and associated with high toxicity and side effects, development of alternative approaches is imperative. The importance of dendritic cells (DCs) in immunity against tumours is now well established. DC immunotherapy for melanoma is possible but must be considered in terms of effectiveness and clinical viability. The source of DCs to be used in adoptive therapy as well as the nature and method of delivery of the priming antigen are important factors. The most suitable DC appears to be cells derived by culture from hemopoietic progenitor cells (HPC) in bone marrow or DC progenitors in peripheral blood. Generation of an effective anti-tumour immune response will be dependent upon the presentation of multiple melanoma-specific antigens by both major histocompatibility complex (MHC) class I and class II molecules and stimulation of both tumour-specific cytotoxic T lymphocytes (Tc) and T helper type 1 (Thl) cells. Different techniques for delivery of the priming antigen offer different advantages. DCs can be pulsed with peptide, protein or tumour cell lysate, transfected with viral vectors or naked nucleic acid and tumour/DC hybridomas can also be generated. Repeated antigen administration into neighbouring lymph nodes appears to be the most effective method for promoting a systemic anti-tumour response. Adjuvant therapies can also enhance immune responses and lead to total tumour clearance. The importance of DC immunotherapy in clinically different stages of disease will also be an important consideration.