Treatment of transplanted rat tumours with double-stranded RNA (BRL 5907). I. Influence of systemic and local administration

Abstract

Summary.-Growth of transplanted rat tumours was retarded and in some cases completely suppressed when cells were injected subcutaneously in admixture with double stranded RNA (ds-RNA). This response required intimate contact between ds-RNA and tumour cells and systemic treatment with the agent failed to prevent progressive growth of a range of rat tumours. Direct cytotoxic effects of ds-RNA may contribute to tumour suppression since the compound was cytotoxic in vitro for cultured tumour cells. The involvement of host factors is suggested, however, by the in vivo tests showing variations in susceptibility to ds-RNA mediated tumour suppression similar to that previously observed with bacterial adjuvants.

Localized irradiation of tumors prior to synthetic dsRNA therapy enhanced the resultant anti-tumor activity

“…This finding may also explain the stronger anti-tumor activity observed when the pI:C/LP was peritumorally injected in the combination therapy than when they were injected into a site distal to the tumors (Fig. 3B), in agreement with a previous finding that the poly(I:C) was more efficacious when given locally [19,41,42]. However, more convincing evidence supporting that the type I IFNs contributed significantly to the combined anti-tumor activity was shown in Fig.…”

Cytotoxic Activity of Human Dendritic Cells Is Differentially Regulated by Double-Stranded RNA and CD40 Ligand

“…Finally, TRAIL induction by poly(I:C) is shown to be dependent on IFN-␤ production in DCs, in agreement with Liu et al (11) who reported the induction of a TRAIL-mediated tumoricidal activity in monocyte-derived DCs treated with rIFN-␤. More than 20 years ago, poly(I:C) was reported to stimulate macrophage tumoricidal activity (44) and to induce tumor regression in vivo (45,46) through unidentified mechanisms. Our data suggest that TRAIL induction by poly(I:C) may partly account for the antitumoral activity of this molecule.…”

Inhibitory effect of the polyinosinic‐polycytidylic acid/cationic liposome on the progression of murine B16F10 melanoma

“…Although various researchers have examined polyinosinic-polycytidylic acid (PIC), a synthetic doublestranded polyriboneucleotide (dsRNA), for its tumor suppressive effects (reviewed by Pimm et al [1]), it is still controversial whether PIC can be clinically used for suppressing tumor growth or inhibiting tumor development by activating the host immune system. In particular, the effects of systemic PIC on the development of experimental tumors, even in murine tumor models, were questioned by several papers [1][2][3], which suggested that such effects largely depended on the direct cytotoxic effects of PIC on tumor cells and host factors.…”

“…In particular, the effects of systemic PIC on the development of experimental tumors, even in murine tumor models, were questioned by several papers [1][2][3], which suggested that such effects largely depended on the direct cytotoxic effects of PIC on tumor cells and host factors. In contrast, the local administration of PIC has been demonstrated to be effective in tumor suppression [1,4,5].…”