Hiltonol

Summary

Hiltonol (poly-ICLC) is a synthetic double-stranded RNA adjuvant and immunostimulant developed by Oncovir. It is under investigation primarily as a vaccine adjuvant in cancer immunotherapy (e.g., glioblastoma, melanoma) and infectious disease vaccines. It has been explored in HIV, West Nile virus, and SARS-CoV-2 vaccine platforms. It is not currently FDA-approved for any indication but has been used in numerous clinical trials.

Mechanism of Action

Hiltonol is a stabilized formulation of polyinosinic-polycytidylic acid complexed with poly-L-lysine and carboxymethylcellulose (poly-ICLC). It activates Toll-like receptor 3 (TLR3) and cytosolic RNA helicases (MDA5/RIG-I), stimulating innate immune signaling, type I interferon production, and dendritic cell maturation, thereby enhancing both cellular and humoral adaptive immune responses.

Routes of Administration

Goals & Uses

• Antitumor activityOncologyLow
• Neuroprotection/neuroimmune modulationNeurologyLow
• Innate immune activationImmunostimulationHigh
• Infectious disease vaccine adjuvantVaccinologyModerate
• Cancer vaccine adjuvantImmunotherapyModerate

Contraindications

• Known hypersensitivity to poly-ICLC componentsAllergicHigh
• Active severe systemic infectionInfectiousModerate
• Severe autoimmune diseaseImmunologicalHigh

Adverse Effects

• Flu-like symptomsSystemic/ImmunologicalCommon
• Cytokine release syndromeImmunologicRareSystemic inflammatory response from immune activation
• Injection site reactionsLocalCommon
• HeadacheNeurologicCommonPain in the head or upper neck
• FatigueGeneralCommonLow energy or tiredness
• Elevated liver enzymes (transaminases)HepaticUncommon

Drug Interactions

• Anticoagulants (e.g., warfarin)Low
• Immunosuppressants (e.g., corticosteroids, cyclosporine)Moderate
• Other TLR agonists / immunostimulantsModerate

Population Constraints

• Pediatric patientsAgeRelative
• Elderly patients (>75 years)AgeRelative
• Pregnant or breastfeeding womenReproductiveRelative
• Patients with severe hepatic impairmentHepaticRelative

Regulatory Status

• European UnionInvestigationalNo EMA approval; available only in clinical trial settings.
• United StatesInvestigationalUsed exclusively under IND applications; not FDA-approved. Orphan Drug Designation obtained for certain indications.
• United KingdomInvestigationalNo MHRA approval; investigational use only.

Not FDA-approved; used under IND applications in clinical trials. Designated as an investigational product by Oncovir, Inc. Has received Orphan Drug Designation for certain oncology indications. Available to qualified researchers under IND.

Evidence & Sources

No sources recorded yet.