hTERT-encoding DNA vaccine INVAC-1

Drug Overview

The hTERT-encoding DNA vaccine INVAC-1 (also known simply as INVAC-1) is an investigational, therapeutic cancer vaccine designed to mobilize the body’s immune system against malignant cells. It targets the human telomerase reverse transcriptase (hTERT), the catalytic subunit of the enzyme telomerase. Telomerase is often called the “immortality enzyme” because it allows cells to divide indefinitely, a hallmark of cancer.

Developed by Invectys, INVAC-1 is a DNA plasmid, a small, circular piece of DNA, that carries the genetic instructions for a modified, inactive version of the hTERT protein. In the oncology landscape of 2024–2026, INVAC-1 is recognized as a leading candidate in the field of “universal” cancer vaccines because hTERT is overexpressed in approximately 85–90% of all human cancers, regardless of the organ of origin.

• Generic Name: INVAC-1 (Tirvalimogene teraplasmid).
• Drug Class: Therapeutic DNA Vaccine / Active Immunotherapy.
• Target: hTERT (Human Telomerase Reverse Transcriptase).
• Platform: DNA Plasmid with Ubiquitin-fusion technology.
• Route of Administration: Intradermal (ID) injection followed by Electroporation.
• FDA Approval Status: Investigational. As of March 2026, INVAC-1 is not FDA-approved. It has successfully completed a First-in-Human Phase I trial (NCT02301754) and has been studied in various solid tumors and hematologic malignancies.

What Is It and How Does It Work? (Mechanism of Action)

INVAC-1 works by “re-educating” the immune system to recognize telomerase as a foreign threat rather than a normal part of the body.

1. The Role of Telomerase in Cancer

Normal adult cells have a limited lifespan because their telomeres (the caps on the ends of chromosomes) shorten every time the cell divides. When telomeres get too short, the cell dies. Cancer cells bypass this by overproducing hTERT, which rebuilds the telomeres, effectively making the cancer cell immortal. INVAC-1 aims to turn this survival mechanism into a target.

2. Molecular Level Mechanisms

• Electroporation-Assisted Delivery: Because DNA plasmids do not easily enter cells on their own, INVAC-1 is administered using an electroporation device. This device sends brief, controlled electrical pulses into the skin, creating temporary “nanopores” in cell membranes that allow the DNA to flood into the cells.
• Ubiquitin Fusion (The “Death Tag”): The INVAC-1 plasmid is engineered so that the hTERT protein it produces is fused to ubiquitin. Ubiquitin is a natural molecule that acts as a “trash tag.”
• Proteasomal Processing: This tag directs the hTERT protein straight to the cell’s proteasome (the cellular shredder), where it is broken down into small fragments called peptides.
• MHC Class I Presentation: These hTERT fragments are then displayed on the cell surface by MHC Class I molecules, acting like “wanted posters” for the immune system.
• T-cell Activation: This high-efficiency presentation triggers a massive expansion of CD8+ Cytotoxic T-lymphocytes and CD4+ Th1 Helper T-cells that are specifically programmed to hunt and kill any cell in the body displaying hTERT.

FDA Approved Clinical Indications

There are currently no FDA-approved indications for INVAC-1.

Clinical research has focused on “pan-cancer” applications due to the near-universal expression of telomerase in tumors:

• Advanced/Refractory Solid Tumors: Including lung, breast, colorectal, and prostate cancers that have failed standard-of-care treatments.
• Hematologic Malignancies: Specifically investigated in high-risk Chronic Lymphocytic Leukemia (CLL).
• Minimal Residual Disease (MRD): Investigated as a way to “clean up” microscopic cancer cells remaining after surgery or chemotherapy to prevent relapse.

Dosage and Administration Protocols

The dosing of INVAC-1 was established during the Phase I dose-escalation study to find the “Optimal Biological Dose”, the amount needed to trigger a maximum immune response without causing undue stress to the patient.

Clinical Efficacy and Research Results

As of 2024–2026, clinical data suggests that INVAC-1 is a potent “immune-stabilizing” agent.

• Disease Control Rate: In the Phase I study of 26 patients with advanced solid tumors, 58% of patients achieved Stable Disease (SD). Some patients with metastatic disease remained stable for over 9 months, which is significant for a heavily pre-treated population.
• Immune Response Rate: The vaccine successfully induced hTERT-specific T-cell responses in 63% of evaluable patients. These responses were “polyfunctional,” meaning the T-cells produced multiple cytokines (like IFN-$\gamma$ and TNF-$\alpha$) to attack the tumor.
• Treg Reduction: Researchers observed a decrease in Regulatory T-cells (Tregs) following vaccination. Tregs are cells that cancer uses to “hide” from the immune system, so their reduction is a positive clinical sign.
• Safety Longevity: Follow-up data has shown that the immune “memory” created by the vaccine can last for several months after the final dose.

Safety Profile and Side Effects

INVAC-1 is generally much better tolerated than chemotherapy because hTERT is rarely found in healthy adult tissues.

Common Side Effects (>20%):

• Injection Site Reactions: Redness, itching, or a small, firm bump (granuloma) at the site of the electroporation.
• Asthenia (Fatigue): A general sense of tiredness, usually lasting 24–48 hours after the injection.
• Procedural Pain: The electroporation pulses feel like a series of “sharp stings” or muscle twitches, but the sensation lasts only a few seconds.

Serious Risks and Monitoring:

• Autoimmunity: Because hTERT is expressed in some normal stem cells (like those in bone marrow), doctors monitor for bone marrow suppression (low blood counts). However, significant autoimmune damage has not been observed in trials.
• Syncope: Rare instances of fainting or lightheadedness immediately following the electroporation procedure.

Research Areas

In the fields of Stem Cell and Regenerative Medicine, INVAC-1 is a central tool for studying the “Telomerase Niche.” Since telomerase is required for the long-term survival of healthy stem cells, researchers are using INVAC-1 to determine the “threshold” of immune attack. They are investigating whether the vaccine can selectively kill Cancer Stem Cells (which have very high telomerase levels) while sparing healthy Hematopoietic Stem Cells (which have lower, tightly regulated levels). This research is vital for ensuring that cancer vaccines do not inadvertently accelerate the aging process in healthy tissues.

Patient Management and Practical Recommendations

Pre-treatment Tests:

• Baseline Blood Counts (CBC): To ensure normal bone marrow function before starting the vaccine.
• hTERT Expression Analysis: Although 90% of cancers express hTERT, a biopsy is often used to confirm the target is present.
• EKG: To ensure the patient can safely undergo the brief electrical pulses of electroporation.

Precautions:

• Device Interference: Electroporation should be avoided near implanted electronic devices like pacemakers or defibrillators.
• Steroid Avoidance: Patients should avoid high-dose corticosteroids, as these can kill the very T-cells the vaccine is trying to create.

“Do’s and Don’ts” List:

• DO expect a “pulsing” sensation during the delivery; it is a sign that the DNA is successfully entering your cells.
• DO keep the injection site clean and dry for 24 hours to prevent irritation.
• DON’T apply topical steroid or anti-inflammatory creams to the injection site, as this can dampen the local “alarm” signal needed to start the immune response.
• DON’T miss your Day 15 and Day 29 boosters; the “priming” phase is the most critical part of building long-term immunity.

Legal Disclaimer

The information provided is for educational and informational purposes only and does not constitute medical advice. hTERT-encoding DNA vaccine INVAC-1 is an investigational agent and is not currently approved by the US FDA for any indication. Access is limited exclusively to registered clinical trials. Always consult with a qualified oncologist regarding your diagnosis and eligibility for participation in research.