Prevention of metastatic spread by postoperative immunotherapy with virally modified autologous tumor cells. I. Parameters for optimal therapeutic effects

Abstract

Effective anti-metastatic therapy was achieved in a mouse tumor model by combining surgery with post-operative immunotherapy using virus-modified autologous tumor cells. No therapeutic effect was observed when using for immunotherapy the nonmodified autologous tumor ESb, which is only weakly immunogenic and highly metastatic. The viral modification was achieved by infecting the tumor with an avirulent strain of Newcastle disease virus (NDV), which led to expression of viral antigens and to an increase in the tumor cells' immunogenicity. Parameters which were of decisive influence for success or failure of therapy were the time of operation of the primary tumor and the dose of virus which was admixed to a standard dose of irradiated tumor cells. There was a low dose optimum of NDV at about 100 hemagglutinating units per 25 X 10(6) tumor cells. The therapeutic effect observed was less pronounced if the virus was given separately from the tumor cells. Post-operative immunotherapy with NDV-modified tumor cells had the following therapeutic effects: (1) disappearance of micrometastases from visceral organs as ascertained by a sensitive bioassay; (2) life prolongation in virtually all animals when compared to controls (operated only); (3) cures in about 50% of the treated animals. The possible mechanism of this therapeutic effect and its potential for clinical application are discussed.