Phase I clinical trial with IL-2-transfected xenogeneic cells administeredin subcutaneous metastatic tumours: clinical and immunological findings

Various studies have emphasized an immunodepression state observed at the t umour site. To reverse this defect and based upon animal studies, we initia ted a phase I clinical trial of gene therapy in which various doses of xeno geneic monkey fibroblasts (Vero cells) genetically engineered to produce hu man IL-2 were administered intratumorally in 8 patients with metastatic sol id tumours. No severe adverse effect was observed in the 8 patients analyse d during this clinical trial even in the highest dose (5 (sic) = 107 cells) group. This absence of toxicity seems to be associated with rapid eliminat ion of Vero-IL-2 cells from the organism. Indeed, exogenous IL-2 mRNA could no longer be detected in the peripheral whole blood 48 hours after Vero-IL -2 cell administration. In addition, we did not find any expression of exog enous IL-2 mRNA in post-therapeutic lesions removed 29 days after the start or therapy. A major finding of this trial concerns the two histological re sponses of two treated subcutaneous nodules not associated with an apparent clinical response. The relationship between local treatment and tumour reg ression was supported by replacement of tumour cells by inflammatory cells in regressing lesions and marked induction of T and natural killer cell der ived cytokines (IL-2, IL-4, IFNg ...) in post-therapeutic lesions analysed 28 days after the start of Vero-IL-2 administration. Gene therapy using xen ogeneic cells as Vehicle may therefore present certain advantages over othe r vectors, such as its complete absence of toxicity. Furthermore, the in vi vo biological effect of immunostimulatory genes, i.e IL-2-, may be potentia ted by the xenogeneic rejection reaction, (C) 2000 Cancer Research Campaign http://www.bjcancer.com.