Newcastle disease virus therapy of human tumor xenografts: antitumor effects of local or systemic administration

Previously we showed that a single local injection of the avian paramyxovir us Newcastle disease virus (NDV) strain 73-T caused long-lasting, complete tumor regression of human neuroblastoma and fibrosarcoma xenografts in athy mic mice. Here we report the antitumor effects of NDV administered by eithe r the intratumoral (IT) route to treat a variety of human carcinoma xenogra fts or by the systemic (intraperitoneal, IP) route to treat neuroblastoma x enografts (6.5-12 mm in diameter). For IT treatments, mice were randomized into treatment groups and given a single IT injection of NDV 73-T, vehicle (phosphate buffered saline, PBS), or UV-inactivated NDV. For systemic thera py, mice (n = 18) with subcutaneous IMR-32 human neuroblastoma xenografts r eceived IP injections of NDV (5 X 10(9) PFU). Significant tumor growth inhi bition (77-96%) was seen for epidermoid (KB8-5-11), colon (SW620 and HT29), large cell lung (NCIH460), breast (SKBR3), prostate (PO), and low passage colon (MM17387) carcinoma xenografts treated IT with NDV. In all cases, tum ors treated IT with PBS or replication-incompetent, UV-inactivated NDV disp layed rapid tumor growth. After a single IP injection of NDV, complete regr ession of IMR-32 neuroblastomas was observed in 9 of 12 mice without recurr ence for the 3-9 month follow-up period. Six mice with recurrent neuroblast omas after one IP injection received one to three additional IP treatments with NDV. Three of these six mice showed complete regression without recurr ence. These data show that: (1) NDV administered either IT or IP is an effe ctive antitumor therapy in this system, (2) replication competency is neces sary for maximal effect, and (3) multiple NDV doses can be more effective t han a single dose. These studies provide further rationale for the preclini cal study of NDV as an oncolytic agent. (C) 2001 Elsevier Science Ireland L td. All rights reserved.