Local immunotherapy of cancer with interleukin 2

Abstract

During the past decade it has become increasingly evident that the manifestation of antitumour immunity is a result of intricate communications and interactions among various cell populations of the immune system derived from the regulatory and cytotoxic T cell, macrophage, and B cell lineage. Cell-to-cell messages mediated by T helper cellreleased soluble products were shown to induce a substantial augmentation of antitumour immunity and to play an important role in defence against neoplasias. A pivotal role in this respect was ascribed to interleukin 2 (IL-2). IL-2 has been defined as a class of phylogenetically well-conserved potent immunoregulatory molecules that trigger the clonal expansion of antigenor mitogen-activated T cells in culture [1, 2]. Signals emanating from the T cell antigen-receptor complex or transduced after binding of some other mitogenic T cell ligands coordinate the transcriptional activation of both the IL-2 gene and the genes encoding IL-2 receptors. Activation of the T cell antigen-receptor complex renders T cells competent to receive the cell cycle signals mainly by inducing the formation of high-affinity IL-2 receptors [3]. Binding of IL-2 to the high-affinity receptors promotes movement of the T cells through the restriction point of the cell cycle enabling the cell G~ progression and S phase transition. In other words, antigen-stimulated T cells undergo Go to G~ transition but do not progress through G~ to S phase unless IL-2 is provided [3]. In this way, IL-2