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A class of cell-killing chemotherapeutic agents seems to have an additional benefit. The drugs help prompt the immune system to turn against the tumor (pages 54–61).

Cytotoxic T lymphocytes (CTLs) kill neoplastic or virally infected cells after recognizing on their surface antigenic peptides bound to major histocompatibility complex class I molecules. These peptides are derived from antigens that are degraded in the cytosol of the affected cell. Because exogenous proteins cannot enter the cytosol, immunizations with killed pathogens or their proteins do not generally elicit CTLs. However, antigens that are internalized into phagocytic cells can enter the cytosol and be processed for class I presentation. Here we show that immunization with a purified antigen on an avidly phagocytized particle primes CTLs, which in turn protect animals from subsequent challenge with tumours transfected with the antigen gene. Interestingly, these animals also become immune to other antigens expressed by the tumour. This approach could be exploited to develop tumour and viral vaccines.

Delivery of antigen in a manner that induces effective, antigen-specific immunity is a critical challenge in vaccine design. Optimal antigen presentation is mediated by professional antigen-presenting cells (APCs) capable of taking up, processing and presenting antigen to T cells in the context of costimulatory signals required for T-cell activation. Developing immunization strategies to optimize antigen presentation by dendritic cells, the most potent APCs, is a rational approach to vaccine design. Here we show that cutaneous genetic immunization with naked DNA results in potent, antigen-specific, cytotoxic T lymphocyte-mediated protective tumor immunity. This method of immunization results in the transfection of skin-derived dendritic cells, which localize in the draining lymph nodes. These observations provide a basis for further development of DNA-based vaccines and demonstrate the feasibility of genetically engineering dendritic cells in vivo.

Pathogen-derived 'helper' sequences promote anti-tumor immune responses induced by a naked DNA vaccine ( ).