Toll-like receptor-3 as a target to enhance bioactivity of cancer immunotherapy

Abstract

The purpose of this study was to explore the potential of toll-like receptor-3 stimulation, with polyI:C(12)U (poly[l].poly[C(12),U]; rintatolimod [Ampligen; Hemispherx Biopharma, Philadelphia, PA]) to enhance bioactivity of cancer immunotherapies.Several models of immune activation were assessed with polyI:C(12)U at concentrations that were achieved clinically. Dendritic cell maturation and antigen-specific immune responses were evaluated in vitro and in a murine model. The potential for polyI:C(12)U to enhance antibody-dependent cellular cytotoxicity against tumor was also evaluated.Dendritic cells are matured and T-cell stimulation is enhanced in the presence of polyI:C(12)U. In addition, polyI:C(12)U induced the release of proinflammatory chemokines and cytokines. Prostate-specific antigen-specific T-cell and antibody responses were enhanced significantly in a BALB/c prostate-specific antigen transgenic mouse model. Finally, rituximab-mediated antibody-dependent cellular cytotoxicity against tumor targets was improved significantly by the addition of polyI:C(12)U.PolyI:C(12)U shows promise as a potential agent for selective enhancement of effect with currently available and future cancer immunotherapies.

View details for DOI 10.1016/j.ajog.2009.12.001

View details for Web of Science ID 000278534200038

View details for PubMedID 20080226