Cell-based cancer gene therapy: breaking tolerance or inducing autoimmunity?

This review examines the mechanisms involved in anti-tumor immunity and how peptides present in many tumor types (tumor-associated antigens) are recognized by T cells from tumor-bearing cancer patients. Tumor-associated antigens are derived from proteins that are also expressed in normal cells. It is predicted that immune responses to such peptides will be compromised by self-tolerance or that stimulation of effective immune responses will be accompanied by autoimmunity. We also consider that the immunity induced against two autoantigens, which are highly conserved in vertebrates, involve qualitatively different mechanisms, such as the production of antibodies and cell-mediated immune responses. However, both pathways lead to tumor immunity and identical phenotypic manifestations of autoimmunity. Appropriate selection of the optimal tumor antigen is critical for the induction of an anti-tumor immune response. Thus, we stress that the methods for antigen presentation using dendritic cells play a critical role in the development of tumor vaccines, to break immune tolerance and induce a strong immune response against them. The viability and feasibility of expansion of canine dendritic cells from bone marrow and peripheral blood ex vivo for the treatment of spontaneous cancers in dogs is also discussed.