The antitumor effects of human lymphoblastoid interferon on human renal cell carcinoma in athymic nude mice.

The antitumor effects of human lymphoblastoid interferon (HLBI) on human renal cell carcinomas transplanted in nude mice, i.e., KU-2 and RCC-1, were investigated and compared with those on other human tumors, viz. HeLa (cervical carcinoma), KB (nasopharyngeal carcinoma), H.Ep#2 (laryngeal carcinoma), and MX-1 (breast cancer). A pharmacokinetic study on HLBI was also carried out in non-tumor-bearing nude mice. HLBI therapy was performed with a dose of 10(5) IU/mouse by daily SC or IT (intratumoral) injection for 2-4 weeks. Two renal cell carcinomas, KU-2 and RCC-1, proved to be highly sensitive to HLBI. The growth of these tumors was inhibited not only by IT but also by SC injection of HLBI. In contrast, HLBI exerted only a slight effect or none at all on the other human tumors, namely, MX-1, KB, H.Ep#2, and HeLa, even when given by IT injection. The data show that the antitumor effects of HLBI depend on the types of human tumors and may be relevant to the clinical observation that renal tumors are sensitive to HLBI. The serum HLBI reached a peak level of 4,390 U/ml 1 h after a single SC injection at a dose of 10(5) IU/mouse and declined with a half-life of 4 h to 128 U/ml 24 h later. This time-course was not affected by 10 consecutive daily injections of HLBI. In nude mice, the consecutive administration of HLBI at this dose level appears to result in neither accumulation nor rapid clearance due to antibody formation. From this range of serum HLBI levels and its in vitro anticellular activity, the in vivo antitumor effects of HLBI in nude mice seemed to depend on its direct anticellular action.