Newcastle Disease Virus, Part 2

by National Cancer Institute

(Page 2 of 2)

Studies Using Oncolysate Vaccines

Four clinical trials in the United States studied the use of NDV oncolysates in patients with metastatic melanoma. Three of these studies, a phase I clinical trial and 2 phase II clinical trials, were by the same group of researchers. Some positive results were found in these studies. The fourth trial was led by different researchers and showed no benefit. The same type of NDV was used to make the vaccines in all 4 studies, but the 2 groups of researchers used different methods to make them. Results from these studies need to be confirmed by randomized controlled trials that enroll larger numbers of people.

Two other phase II trials of NDV oncolysates were done in Germany. One of the studies showed that people in the trial had longer disease-free survival when compared with published information on similar patients who were treated with surgery alone. Because these studies were not controlled and the patients received other treatments, it is not clear if it was the treatment with NDV oncolysates that caused the responses reported.

Studies Using Whole-cell Vaccines

All published clinical studies of whole-cell vaccines with NDV have been done in Germany. Most of these studies involved patients with colorectal cancer, breast cancer, ovarian cancer, or renal cell (kidney) cancer. The same type of NDV was used to make the vaccines in all of the studies.

Some of these studies found improved disease-free survival or improved overall survival in patients treated with whole-cell vaccines. The lack of control groups and other weaknesses in study design and reporting made it unclear if benefits were caused by the whole-cell vaccine or by something else. Overall, the results showed that these vaccines may help the immune system kill more cancer cells during the vaccination program but may not provide long-term cancer immunity.

Studies Involving Infection with NDV (Including MTH-68)

Most research on the treatment of cancer by infecting patients with NDV has been done in Hungary, using the NDV strain MTH-68. The published findings include the following types of studies:

• An anecdotal report (incomplete descriptions of the medical and treatment history of one or more patients).

• A case report (a detailed report of the diagnosis, treatment, and follow-up of an individual patient).

• A small case series (a group of case reports involving patients who were given similar treatment).

• A phase II clinical trial.

According to the researchers, the MTH-68 treatment was helpful for most of the patients in these studies. The number of patients in the studies was small, however, and the patients in the clinical trial were not randomly assigned. The patients also received other treatments. For these reasons, it is not known if the patients were helped by the MTH-68 or by something else.

In the United States, a phase I clinical trial tested PV701, another type of NDV. In this trial, 79 patients with advanced cancers that were not helped by conventional therapy were given PV701 by injection into a vein. Some patients had partial responses to the treatment, while others did not have any change in their condition. More studies are planned.

One major concern is that repeated injections of NDV may cause a person's immune system to form antibodies against the virus. These antibodies would prevent NDV from infecting and killing cancer cells. More research is needed to study this.

7. Have any side effects or risks been reported from NDV?

The side effects caused by NDV exposure have been mild to moderate. As noted in Question 1 1, NDV causes mild flu-like symptoms, conjunctivitis, and laryngitis in humans. Other side effects vary with how the virus is given.

The most commonly reported side effect after treatment with the virus alone is fever, which usually goes away within 24 hours. In one study, inflammation and swelling were seen near some tumors. These complications may have contributed to the death of one patient.

The most common side effects of treatment with NDV-infected whole-cell vaccines are minor:

• Mild headache.
• Mild fever on the day of the vaccination.
• Itching, swelling, and redness of the skin at the injection site.

The only negative effect of treatment with the NDV oncolysate vaccine is inflammation at the injection site.

Studies that combined treatment with NDV oncolysates or whole-cell vaccines with substances called cytokines reported flu-like symptoms, fever, and swelling. The side effects seen in these studies have been linked to the cytokine portion of the treatment.

8. Is Newcastle disease virus approved by the US Food and Drug Administration (FDA) for use as a cancer treatment in the United States?

The US Food and Drug Administration (FDA) has not approved Newcastle disease virus as a treatment for cancer.

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