Gene therapy study of cytokine-transfected xenogeneic cells (Vero-interleukin-2) in patients with metastatic solid tumors

On the basis of compelling preclinical data in cats and dogs, we initiated a clinical gene therapy study in nine patients with advanced solid tumors u sing xenogeneic fibroblasts secreting human interleukin (IL)-2 (Vero-IL-2 c ells). Cohorts of three successive patients with tumors accessible to compu ted tomography- or ultrasound-guided injection were treated repeatedly with 5 x 10(5), 5 x 10(6), or 5 x 10(7) Vero-IL-2 cells. The endpoints of the s tudy were feasibility, toxicity, and the clinical and biological effects of this novel approach to immunotherapy of cancer. Histopathological, immunol ogical, and molecular analyses were performed on biopsy specimens of tumors and blood samples before, during, and after treatment, Treatment was well tolerated, and toxicity consisted of transient fever in one patient and sho rt-lived, mild itching and erythema in two others. One patient with soft-ti ssue sarcoma showed a reduction of >90% and >50% of the volume of two dista nt, noninjected metastases, lasting for 29+ and 26 months, respectively. Fo ur other patients showed stabilization of their disease for 3-9 months; of these patients, one with melanoma developed marked vitiligo. We conclude th at repealed injections of less than or equal to 5 x 10(7) Vero-IL-2 cells a re feasible and safe in heavily pretreated patients with advanced solid tum ors. An additional evaluation of an intratumoral application of Vero-IL-2 s eems warranted.