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


METHODS
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.


RESULTS
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.


CONCLUSIONS
PolyI:C(12)U shows promise as a potential agent for selective enhancement of effect with currently available and future cancer immunotherapies.
Nicodemus
Christopher F
CF
Advanced Immune Therapeutics, Inc., Medford, MA, USA.
Wang
Lin
L
Lucas
Julie
J
Varghese
Bindu
B
Berek
Jonathan S
JS
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D058846:Antibodies, Monoclonal, Murine-Derived; D019496:Cancer Vaccines / Q000276:immunology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D051379:Mice; D017430:Prostate-Specific Antigen / Q000276:immunology; D000069283:Rituximab; D013601:T-Lymphocytes / Q000276:immunology; D051196:Toll-Like Receptor 3 / Q000276:immunology*
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D019496:Cancer Vaccines; D016207:Cytokines; D051196:Toll-Like Receptor 3; D000069283:Rituximab; D017430:Prostate-Specific Antigen