From the FDA Drug Label
CLINICAL PHARMACOLOGY Mechanism of Action In non-clinical pharmacology studies, tigilanol tiglate has been shown to have three inter-related effects that are responsible for its anti-tumor effectiveness. The first effect is to cause oncolysis of tumor cells that are in direct contact with tigilanol tiglate The oncolysis occurs within the first hours following treatment and results from the disruption of mitochondrial functioning. Secondly, at the same time, tigilanol tiglate activates a protein kinase C (PKC) signaling cascade which propagates throughout the tumor, resulting in an acute inflammatory response with swelling and erythema extending to the tumor margins and immediate surroundings This inflammatory response is normal and necessarily contributes to the activity of tigilanol tiglate by (a) restricting blood and oxygen supply to the tumor (causing localized hypoxia) and (b) recruiting and activating innate immune cells (principally neutrophils and macrophages), which then target the tumor and release reactive oxygen species, proteases, and cytokines that function in an antimicrobial role. The third component of the antitumor activity of tigilanol tiglate is associated with direct effects of the drug in increased permeability of the tumor vasculature (via activation of the Beta-II isoform of PKC) leading to tumor vascular destruction
The role of EBC-46 (Tigilanol Tiglate) in cancer treatment is to:
- Cause oncolysis of tumor cells
- Activate a protein kinase C (PKC) signaling cascade, resulting in an acute inflammatory response
- Increase permeability of the tumor vasculature, leading to tumor vascular destruction 1
From the Research
EBC-46 (tigilanol tiglate) is a promising experimental cancer treatment that induces immunogenic cell death and enhances the response of both target and non-injected tumors to immune checkpoint blockade, as shown in a recent study published in the Journal for Immunotherapy of Cancer 2.
Mechanism of Action
The compound works by rapidly destroying tumor blood vessels and directly killing cancer cells through protein kinase C activation, typically causing tumor destruction within 24-48 hours after direct injection into the tumor.
- It induces the death of endothelial and cancer cells at therapeutically relevant concentrations via a caspase/gasdermin E-dependent pyroptotic pathway.
- It acts as a lipotoxin, binding to and promoting mitochondrial/endoplasmic reticulum (ER) dysfunction, leading to unfolded protein response mt/ER upregulation, with subsequent ATP depletion, organelle swelling, caspase activation, gasdermin E cleavage, and induction of terminal necrosis.
Clinical Trials and Efficacy
Clinical trials in humans are ongoing, with early studies showing potential effectiveness against melanoma, head and neck cancers, and other solid tumors.
- A Phase I dose-escalation study found that intratumoral tigilanol tiglate was generally well tolerated, and clinical activity was observed in 9 tumor types, including complete response in four patients 3.
- Another study found that tigilanol tiglate-induced changes in secretome profiles alter C-Met phosphorylation and cell surface protein expression in H357 head and neck cancer cells, further contributing to our understanding of the mode of action and efficacy of TT in the treatment of solid tumors 4.
Side Effects and Availability
Side effects include pain at the injection site, inflammation, and potential wound formation as the tumor breaks down.
- While early results are encouraging, EBC-46 is not yet available as a standard cancer treatment for humans, and patients interested in this therapy would need to explore clinical trial participation through their oncologists.
- The compound is particularly interesting because it appears to work through a novel mechanism different from conventional chemotherapy, potentially offering a new approach for certain difficult-to-treat cancers.