Introduction

Although new chemotherapeutic agents, increased doses, combinations of drugs, or even high-dose ablative regimens have been used with some success, their use is ultimately limited by their nonspecific end-organ toxicity. So, investigators have explored strategies of anti-neoplastic treatment with the potential to specifically kill malignant cells, circumventing tumour-cell resistance and using a different mechanism from conventional chemotherapy. These so-called 'biological' therapies of cancer aim to produce anti-tumour effect through the activation of defence mechanisms of the host or the administration of natural substances. It was the development of molecular biology and hybridoma technology that made available the unlimited supply of appropriate reagents.

The concept of a role for the immune response in the control or even eradication of cancer is not new. In fact, it was as early as in 1891 that William Coley reported tumour regression after stimulation of the patient's immune system by deliberately infecting cancer patients with erysipelas. But it was not until the 1960s that the 'immune surveillance theory of cancer' was introduced by Burnet. According to this theory, immune system cells continuously patrol the body, eliminating newly mutated malignant cells and protecting against the development of cancer. This vigilance would only be circumvented if the immune system was depressed or malignant cells became more aggressive.

This hypothesis provided the background for the development of cancer immunotherapy, which encompasses all the therapeutic manipulations of the immune system, utilizing any immune-related agents, such as cytokines, cellular or humoral products, vaccine preparations, and transfected genes, with or without immuno-potentiation by drugs or other agents.

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