Cancer: recent development of cell-based immunotherapy

Cancer is one of the leading causes of death: in the year 2007 8 million people died from cancer and 12 million discovered they have cancer.The evolution of cancer therapeutic treatment started in the early 1900 with surgical excision of solid neoplasias, led in the last century to both the radio- and chemotherapeutic approaches, which still have a major role in the management of most tumors.Recently, discovery of tumor antigens, as well as new findings in basic immunology have led to novel opportunities for developing active and specific immunotherapeutical strategies for prevention and treatment of cancer.Evidence from different studies suggests a role for the immune system in the treatment of cancer for the following reasons: tumors are 100 times more likely to occur in people who undergo immunosuppressive regimens than in people with normal immune functions. Conversely, heightened anti-tumor activity of the immune system has been suggested in many reports of spontaneous cancer regression, and a positive correlation between detectable tumor-infiltrating T lymphocytes and patient survival has been observed.Immune defence against tumors is mediated through antigen-specific and nonspecific mechanisms. Cells of the macrophage and NK cell lineage and soluble factors, such as inflammatory cytokines and chemokines play a key defensive role. The antigen specific immune system is based on a division of tasks between T and B cells. However, tumors have developed a number of different direct and indirect strategies to escape immune surveillance, such as loss of tumor antigen expression and enhanced activation of regulatory T cells or immunosuppressive cytokines.The requirement for an efficient immune-based therapy of cancer is the induction of an effective tumor-specific immune response in order to break the immune tolerance to tumor, and to protect the host.In this chapter we discuss the different approaches currently used for immune-based cell cancer therapies, the most important results obtained both in preclinical models and in clinical trials of haematological malignancies and solid tumors, and the strategies for modulation of T regulatory cells.