In Vivo and In Vitro Effects of Xenogeneic Immune Ribonucleic Acid in Patients With Advanced Renal Cell Carcinoma: A Phase I Study

Abstract

Based upon demonstration of repeated prevention of pulmonary metastases by adjuvant immune RNA in animal preparations, xenogeneic immune RNA was given in a phase I study to patients with advanced renal cell carcinoma. Six patients were treated with i.v. infusions of autologous lymphocytes incubated in vitro with immune RNA extracted from splenocytes of guinea pigs immunized with the patient''s own tumor. Serial peripheral blood lymphocytes were obtained during and after each treatment with immune RNA for in vitro evaluation of cell-mediated cytolysis by 51Cr release assay and 125I iododeoxyuridine assay against allogeneic renal cell carcinoma targets and melanoma targets. Neither toxicity nor enhancement of tumor growth was observed. All patients demonstrated significantly increased cell-mediated cytolysis against allogeneic renal cell carcinoma targets but no change against melanoma targets. Increased cell-mediated cytolysis could be demonstrated in individual blood samples after incubation with immune RNA. Progressive in vivo effect was demonstrated in in vitro assay of serial peripheral blood lymphocytes before each successive exposure to immune RNA. Increased cell-mediated cytolysis persisted in peripheral blood lymphocytes up to 9 mo. after therapy. Although without controls 1 patient had complete response and 2 patients had partial responses (8-18 mo.). Two patients had stabilization of the disease for 3-4 mo. and 1 patient had progression of cerebral metastases. One patient is alive 24 mo. after therapy. These results would favor the institution of a randomized prospective trial in patients with advanced renal cell carcinoma or lesser tumor burdens.