VIRUS POTENTIATION OF TUMOR VACCINE T-CELL STIMULATORY CAPACITY REQUIRES CELL-SURFACE BINDING BUT NOT INFECTION

Citation
V. Schirrmacher et al., VIRUS POTENTIATION OF TUMOR VACCINE T-CELL STIMULATORY CAPACITY REQUIRES CELL-SURFACE BINDING BUT NOT INFECTION, Clinical cancer research, 3(7), 1997, pp. 1135-1148
Citations number
68
Categorie Soggetti
Oncology
Journal title
ISSN journal
10780432
Volume
3
Issue
7
Year of publication
1997
Pages
1135 - 1148
Database
ISI
SICI code
1078-0432(1997)3:7<1135:VPOTVT>2.0.ZU;2-H
Abstract
This study elucidates a basically new mechanism of function of a virus -modified tumor cell vaccine which has been successful in mouse tumor models (metastatic ESb lymphoma and B16-F10 melanoma) in preventing or delaying metastatic spread and improving survival and which is being tested in clinical studies. Modification of tumor cells by a low dose of Newcastle disease virus (NDV), which caused this therapy effect, le d to an augmentation of the tumor-specific cytotoxic CD8 T-cell (CTL) response and to increased CD4 T-helper activity in the absence of an a ntiviral T-cell response. When various noninfectious NDV preparations, which, according to newly established quantitative tests, had lost on e or several of the viral functions, were tested, noninfectious virus particles with inactive fusion proteins and virus inactivated by UV li ght, which could fuse but could not replicate, were as active as infec tious NDV in the tumor-specific CTL response. In contrast, NDV inactiv ated hy heat treatment (NDV-HI) had no effect on the CTL response, NDV -HI, even when added to the cultures in excess, did not modulate the a ntitumor CTL response, which argues against a nonspecific adjuvant eff ect. There was no mitogenic effect of NDV. Because NDV-HI was not able to bind to the tumor cell surface and because hemagglutinin-neuramini dase c-DNA transfectants increased antigen-presenting function as viru s-modified cells do, we propose that the NDV effect in the CTL respons e is caused by the introduction of functional viral hemagglutinin-neur aminidase molecules (1000 per virus particle) into the tumor cell surf ace, thereby facilitating cell-cell interactions through their cell-bi nding and neuraminidase activity.