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Dendritic Cell/Peptide Cancer Vaccines: Clinical Responsiveness and Epitope Spreading

Animal models and human clinical trials have clearly documented the ability of cultured, syngeneidautologous dendritic cells (DC) or macrophages to serve as effective immunogcns of anti-tumor CTL in vivo when prepulsed with tumorderived peptide epitopes (1-5). The vaccination of mice with epitope-charged DCs promotes tumor regression and protective immunity against a re-challenge with a normally lethal challenge dose of a tumor expressing the naturally processed and presented epitope used in the vaccine (1) and in some cases, animals rejecting such a tumor challenge were also able to then subsequently reject a challenge with an otherwise identical tumor that fails to express the epitope used in the original vaccination (I). These data support the concept of “epitope spreading”, which may be of crucial interest in the induction of therapeutic immunity against antigenically heterogeous human lesions.