Malignancy: Gene Therapy Vaccines in Acute Myeloid Leukemia : A Need for Clinical Evaluation

In the last decade our understanding of the processes that govern cell growth and differentiation, malignant transformation, and metastasis has become quite sophisticated. These new insights have revolutionized our ability to diagnose and to formulate prognoses for patients with cancer, and have inspired the design and development of novel therapeutic strategies that are based on modern gene-transfer technologies and act at the gene level. Gene therapy, broadly defined as the introduction of genetic material (transgenes) into a patient's cells with an intent to confer a therapeutic benefit, represents the most direct application of recombinant DNA technology in the clinical setting. The challenging concept of modifying the genetic properties of human cells captivated very quickly the interest of clinical and molecular oncologists, and currently, numerous gene therapy clinical trials in cancer patients are under investigation worldwide. Most of these studies involve manipulating the patient's immune response to tumors. The identification of tumor-specific antigens stimulating humoral and cellular responses in cancer patients, together with a better understanding of the molecular mechanisms controlling T cell activation have dramatically accelerated the search for potent cancer vaccines. In this review, we highlight important principles of cancer immunity and cancer vaccines, we discuss critical features of genetic manipulation of tumor cells, and particularly focus on preclinical studies on gene therapy vaccines in acute myeloid leukemia (AML).