Advances in the molecular characterization of human tumors have led to increased interest in the development of targeted therapeutics to include monoclonal antibodies and cancer vaccines. Interest in the development of cancer vaccines has increased since these advances led to the identification of tumor-associated antigens (TAAs).1-3 TAAs expressed by tumors are able to elicit a specific immune response. In addition to having an antigen that serves as a target for the immune response, a successful tumor vaccine requires a platform to present the antigen to the immune system and an environment that is conducive to immune stimulation. The goal of researchers, therefore, has been to identify TAAs and deliver them to the immune system in the context of a vaccine with the appropriate secondary signals required to prompt a robust, protective immune response.
Breast cancer vaccines are appealing because they represent a nontoxic therapeutic modality with great specificity. Another potential benefit of breast cancer vaccines is that they stimulate an immunologic memory response, potentially allowing for a sustained effect without recurrent therapy. In addition, because vaccines are designed to stimulate the immune system, patients are unlikely to develop resistance to this form of targeted therapy. In this chapter, we will review the basics of the immune system's response to vaccination, discuss vaccine formulations, including the TAAs that serve as targets in breast cancer, and present current strategies for incorporating vaccines into treatment algorithms for patients with breast cancer.
The human immune system consists of both innate and adaptive arms. The innate immune system is made up of cells such as mast cells, phagocytes, natural killer cells, basophils, and eosinophils that defend the host in a nonspecific manner. This system provides immediate defense against infection but is unable to confer long-lasting or protective immunity. The major functions of the innate immune system therefore include the recruitment of immune cells to sites of infection or inflammation through release of cytokines, activation of the complement cascade, removal of foreign substances, and activation of the adaptive immune system by antigen presentation. The adaptive immune system then is able to confer long-lasting immunity by mounting 2 types of a response: humoral and cellular. Humoral immunity (the antibody response) involves B cells interacting with a foreign antigen, leading to differentiation into plasma cells or memory cells. Plasma cells are able to secrete specific antibodies against the antigen, while memory cells are longer lasting and function to respond quickly to future exposures of the antigen. Cellular immunity (the T-cell response) involves an interaction between T cells and processed fragments of proteins (peptides) that are present on the surface of other cells in association with major histocompatibility (MHC) molecules.
There are 2 types of MHC molecules: class I and class II (Fig. 91-1). Class I MHC molecules are found on nearly all nucleated cells. They can be loaded with peptides of 8 to 10 amino acids that are generated endogenously within the cytosol ...