Delta-24-GREAT combines direct cancer cell destruction with immune system activation to combat glioblastoma
Glioblastoma, the most common and aggressive form of brain cancer in adults, presents a devastating prognosis. Despite aggressive treatments like surgery, radiation, and chemotherapy, the disease almost invariably recurs, with fewer than 3% of patients surviving five years post-diagnosis 8 . The tumor's ability to evade the immune system, creating what scientists call a "cold" immunologic environment, has been a major obstacle to effective treatment 8 .
Among the most promising developments is a genetically engineered virus known as Delta-24-GREAT, or the GITRL-armed Delta-24-RGD oncolytic adenovirus. This innovative therapy not only directly destroys cancer cells but also uniquely empowers the body's own immune system to launch a sustained attack against the tumor, creating a powerful "double-pronged" assault 1 4 .
5-year survival rate with current treatments
Delta-24-GREAT combines direct oncolysis with immune activation
Genetically modified adenovirus engineered for tumor-selective replication and enhanced cancer cell targeting 3 .
Delta-24-GREAT infects glioma cells and exploits their disrupted regulatory pathways to replicate 1 7 .
Viral replication causes cancer cells to burst, releasing tumor debris containing tumor-associated antigens 6 .
GITRL expression on infected cells provides a powerful "go" signal for T-cells, enhancing their activation and proliferation 4 .
The promising theory was put to the test in a comprehensive preclinical study, the results of which were published in 2019 1 4 . This experiment was critical for demonstrating the virus's effectiveness and understanding how it works.
Immunocompetent mice with implanted glioma cells received single treatments of Delta-24-GREAT, original Delta-24-RGD, or control 1 .
Surviving mice were re-challenged with glioma cells to test for long-term immunity, with controls using melanoma cells to check specificity 1 .
The most dramatic result was the significant extension of survival in mice treated with Delta-24-GREAT compared to those treated with the original virus or a control. Many became long-term survivors 1 .
| Experimental Measure | Result with Delta-24-GREAT | Scientific Importance |
|---|---|---|
| Overall Survival | Significantly prolonged compared to controls and Delta-24-RGD 1 | Demonstrates a direct and powerful therapeutic benefit |
| Response to Tumor Re-challenge | No tumor growth upon re-implantation of glioma cells 1 | Induces long-term, specific immunity, preventing relapse |
| T-cell Infiltration | Increased frequency and activation of CD8+ T cells within tumors 1 4 | Converts "cold" tumors to "hot," enabling immune attack |
| Immune Memory Generation | Increased frequency of central memory CD8+ T cells 1 | Provides the body with a long-term defense force against the cancer |
| Immune Cell Type | Role in Anti-Tumor Immunity | Effect of Delta-24-GREAT Treatment |
|---|---|---|
| CD8+ T cells | Directly recognize and kill cancer cells | Increased infiltration and activation within the tumor 1 4 |
| Central Memory CD8+ T cells | Provide long-term immunity and rapid response upon re-exposure to cancer cells | Frequency is significantly increased, indicating lasting protection 1 |
| CD4+ T cells | "Help" and coordinate the immune response, including supporting CD8+ T cells | Recruitment and activation are enhanced 4 |
Delta-24-GREAT: Significant survival extension
Delta-24-RGD: Moderate improvement
Control: Rapid disease progression
The development of GITRL-armed Delta-24-RGD represents a "vertical advance" in virotherapy, moving beyond a simple cancer-killing virus to a sophisticated cancer-immunotherapy delivery system 1 4 . By combining direct oncolysis with powerful immune co-stimulation, it tackles the dual challenges of tumor bulk and immunosuppression.
The induction of antigen-restricted anti-tumor memory suggests the potential not just to treat the visible tumor, but to create a lasting "vaccine" effect within the body, preventing recurrence 1 .
This work has helped pave the way for the next generation of oncolytic viruses and encourages their combination with other immunotherapies. While the journey from mouse models to a standard treatment for human patients is long and complex, the compelling results surrounding Delta-24-GREAT offer a powerful beacon of hope, illustrating how harnessing and amplifying the body's own defenses could finally turn the tide against glioblastoma.