The role of interleukin-2 in cancer immunotherapy

Abstract

The arena of cellular immunotherapy is an emerging field of study. The field has strong foundations in numerous animal tumor models, which provide avenues of research for refinements in human immunotherapy. Experience from a number of research centers can be generalized: LAK cell trials in humans have demonstrated that PBMCs activated with IL-2 possess reproducible antitumor activity in vitro. Exogenous IL-2 administration to patients is required to maintain the biologic activity of the activated cells, although the requirement for LAK cells in tumors like melanoma is not clear-cut. Overall, the response rate to immunotherapy in humans is approximately 30%. The toxicity of immunotherapy, which is related to the dose of systemic IL-2, can be significantly reduced. The next generation of trials of cellular immunotherapy in humans will use TILs. Murine experiments indicate that this population of cells is more powerful and potentially more specific for tumor than LAK cells. Like LAK cells, TILs also require exogenous IL-2 for optimum performance in vivo. The difficulty in reproducible TIL growth can be overcome by the use of monoclonal antibody activation and IL-2. Improvements in TIL therapy are anticipated from the use of TILs combined with hybrid antibodies, the addition of other biologic response modifiers, and the implementation of genetically engineered cells and cell products.