Immunotherapy of cancer: from vision to standard clinical practice.

Abstract

Until the end of the 19th century the possibility that a tumor could be rejected merely by the body's immune defense was no more than a vision. After more than 100 years of preclinical and clinical research in the field, the vision of cancer immunotherapy became real and has, with multiple tools, successfully entered clinical standard practice. Non-specific mediators of immune defense, such as BCG for treatment of superficial bladder cancer or interferon-alpha for treatment of chronic myelogenous leukemia and hairy cell leukemia, can induce durable remissions. In particular, antigen-specific mediators of immune defense represent promising agents for targeted cancer therapies. Antibody-based treatment of B-cell lymphomas and breast cancer has dramatically improved disease response without major toxicity. A large number of new antibodies targeting different epitopes on a variety of malignant cells are now approaching clinical approval. Allogeneic stem cell transplantation for treatment of leukemia and certain cancers represents the first T cell-based adoptive immunotherapy with large-scale clinical application. Experimental T cell-based immunotherapies with promising clinical perspectives include tumor vaccines, adoptive transfer of autologous tumor-specific effector cells and the genetic transfer of tumor-specific T cell receptors into the patient's lymphocytes. These facts demonstrate that immunotherapy has now been established as the fourth column of cancer therapy besides surgery, radiotherapy, and chemotherapy. On the basis of its already proven efficacy, the usually favorable toxicity profiles and the development perspectives of the experimental approaches a further and more rapid expansion can be expected.