Phase One Trial at UAB Combats Cancer with HSV

By on April 15, 2014
UAB comprehensive Cancer Center has revamped their wing into a technology suite. Updates include a new cyclotron and a state of the art PET imaging in the Advanced Imaging Facility. Flikr/UAB update)

Oncolytic viral therapy is making headlines in cancer research despite the skepticism in both the scientific and popular community.

The idea of intentionally injecting a virus into a human to improve health seems counter-intuitive—just like the notion of vaccinations. However, research has shown that viruses can be modified to infect only cancerous cells that are weaker than normal cells and more susceptible to viral infection.

Once infected, the cancers cells rupture, allowing the virus to spread.  Researchers at UAB are utilizing this oncolytic potential with herpes simplex virus to fight one of the deadliest forms of brain cancer.

Glioblastoma multiforme is the most common primary malignant brain tumor in the United States. Patients are only given 12-15 weeks of life after diagnosis with standard treatment of surgery followed by chemotherapy and radiation.

G207, a modified version of the herpes simplex virus, was identified as a safe viral therapy in two previous studies at UAB. This current research, presented in the April 8 issue of Molecular Therapy, is the first to combine the use of G207 with normal radiation treatment.

Herpes simplex virus often causes a potentially life-threatening swelling in the brain known as encephalitis. The study was conducted with the engineered G207, where the gene responsible for the swelling is removed.

Nine patients received injections of the virus followed by low-dose radiation. No encephalitis occurred and many saw reduction in tumor size and extended survival time.

Two of the nine patients were pleased with the results and requested an additional dose of G207 under compassionate use. Though unexpected, this request opened the possibility for multi-dose treatment in future trials because of the encouraging results of after the second dose in these two patients.

James M. Markert, M.D., Ph.D., professor and chair of the Department of Neurosurgery at UAB and first author on the publication, emphasizes that this was a phase one trial not aimed at establishing efficacy.

Phase one trials feature small testing populations and determine whether the treatment is safe for patients. With the promising results, the project will move to approval for phase two clinical trials. At this point, more subjects will be tested and conditions and protocol will be strictly monitored.

Meanwhile, UAB is investigating the oncolytic potential of M302, another modified herpes simplex virus. IL12, a protein engineered into the virus to induce a stronger immune response, increases anti-angiogenesis that shuts off the vital blood supply to tumor cells.

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    Phase one trials feature small testing populations and determine whether
    the treatment is safe for patients. With the promising results, the
    project will move to approval for phase two clinical trials. At this
    point, more subjects will be tested and conditions and protocol will be
    strictly monitored.

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