Mechanism of Action
: Immune modulator. Tucaresol, a substituted benzaldehyde, is a low-molecular-weight compound that enhances co-stimulatory signaling to CD4-positive T-cells. Immune induction is dependent on transient covalent bonding (Schiff base formation) between carbonyls and amines expressed on antigen presenting cell (APC) and T-cell surfaces. Tucaresol substitutes for the natural donor of carbonyl groups to mimic the transient bonding that is essential for T-cell activation.3-5
In preliminary studies, tucaresol has been shown to stimulate HIV-specific cytotoxic T lymphocyte responses and generation of naive T cells via thymopoiesis in patients receiving antiretroviral therapy (ART) who have suppressed viremia. Tucaresol appears to specifically increase type 1 cytokine production. The clinical benefits of tucaresol use as an adjuvant agent to enhance immune response and restoration in patients receiving ART are still unknown.6-8
: The tucaresol terminal elimination half-life ranged from 105 to 113 hours in a 200-mg single-dose study in healthy men and women who were not HIV-infected. (The investigational drug was administered on two separate occasions, under fed and fasted states).9
: In an analysis of HIV-1 envelope V3 sequences in viral specimens obtained from tucaresol-treated patients in a Phase I/II trial at study entrance and at week 16, tucaresol administration was found to not accelerate V3 evolution.10
Dosing in Clinical Trials
Tucaresol is administered orally.6-8
Phase I/II (HIV-infected treatment-naive and treatment–experienced participants at varying levels of viremia and immunocompetence):
- Pilot study to determine the safety and immunomodulating effects of tucaresol.
Tucaresol was administered according to a pulse dose escalation protocol to patients in four groups: two groups on stable ART and two ART-naive groups, one of which started ART during the study. Pulse dose escalation was initiated with tucaresol 25 mg administered as a single dose during Week 1 and gradual dose increase to tucaresol 100 mg administered once daily for 4 days during Week 12 (approximately 3-week washout between each dose level).6-8
Other clinical trials of tucaresol have also been undertaken.
In the Phase I/II pulse dose escalation study of tucaresol administered over 12 weeks, two tucaresol-related serious adverse events occurred in the first week of treatment: one in a patient taking tucaresol alone and the other in a patient starting both tucaresol and ART. Both serious adverse events involved constitutional signs and symptoms, as well as a decrease in HIV RNA and CD4-positive lymphocytes. After discontinuation of the study drug and administration of either anti-inflammatories or prednisone, all tucaresol-related symptoms subsided and immunovirological abnormalities reverted to prior states.6
No serious adverse events were reported in patients who were receiving tucaresol as an adjuvant to ongoing ART. In this group of patients, the most common adverse events were low-grade fever and mild constitutional symptoms.6
Tucaresol drug interactions are currently unknown.
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. Gazzola L, Marchetti G, Bandera A, et al. Dynamics of T Cells Homeostasis Induced by Tucaresol
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Last Reviewed: April 23, 2014
Last Updated: January 21, 2015