Abstract
A number of studies have demonstrated that inoculation of certain types of cancer cells engineered for expression of the interleukin-2 (IL-2) gene results in reduced tumorigenicity and/or protection from subsequent challenge with a tumorigenic dose of wild-type cells. In the current studies, we have employed murine plasma cell tumors to examine IL-2-mediated tumor rejection as a possible model for therapeutic approaches to human myeloma or plasma cell leukemia. Two murine plasma cell tumor lines, S107 and X24, were infected with a retroviral vector expressing the human IL-2 gene, and the antitumor potential of IL-2-expressing infectants was characterized in syngeneic BALB/c and BALB/c nu/nu mice. Results demonstrate that tumorigenicity of both lines correlates inversely with the amount of IL-2 produced by the tumor cells. However, there are clear differences between the two lines in terms of reduced tumorigenicity and the ability to protect against co-injected parental tumor cells that appear unrelated to IL-2 levels. More importantly, intravenous immunization of animals with irradiated, IL-2 secreting cells from either line leads to significant protection from challenge with highly metastatic parental cells. These results suggest that such an approach may warrant consideration in the treatment of human plasma cell dyscrasias.
Overview summary
The ability of interleukin-2 (IL-2) to modulate tumor development has been assessed in a murine model of multiple myeloma using cell lines that have a number of similarities to the human disease. Irradiated, IL-2-secreting tumor cells induce protection in the majority of animals against a subsequent lethal challenge of parental cells. These results suggest that cytokine-mediated therapy might be considered as an alternative approach to this invariably fatal disease.
Get full access to this article
View all access options for this article.