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This cancer information summary provides an overview of the use of Newcastle disease virus (NDV) as a treatment for people with cancer. The summary includes a brief history of NDV research, a review of laboratory and animal studies, the results of clinical trials, and possible side effects of NDV-based therapy. Several different strains of NDV will be discussed in the summary, including the Hungarian strain MTH (More Than Hope)-68. Information presented in some sections of the summary can also be found in tables located at the end of those sections.
This summary contains the following key information:
Many of the medical and scientific terms used in the summary are hypertext linked (at first use in each section) to the NCI Dictionary of Cancer Terms, which is oriented toward nonexperts. When a linked term is clicked, a definition will appear in a separate window.
Reference citations in some PDQ cancer information summaries may include links to external websites that are operated by individuals or organizations for the purpose of marketing or advocating the use of specific treatments or products. These reference citations are included for informational purposes only. Their inclusion should not be viewed as an endorsement of the content of the websites, or of any treatment or product, by the PDQ Integrative, Alternative, and Complementary Therapies Editorial Board or the National Cancer Institute.
Information presented in this section about the use of Newcastle disease virus (NDV) in the treatment of human cancer is summarized in Table 1 below.
NDV is a paramyxovirus that causes Newcastle disease in a wide variety of birds (most notably, in chickens).[
The genetic material of NDV is RNA rather than DNA.[
There are many different strains of NDV, and they have been classified as either lytic or nonlytic for human cells. Lytic strains and nonlytic strains both appear to replicate much more efficiently in human cancer cells than they do in most normal human cells,[
Another major difference between lytic strains and nonlytic strains is that, although they both have the potential to kill infected cells, the mechanisms by which they accomplish this result are different. The production of infectious progeny virus particles by lytic strains gives them the ability to kill host cells fairly quickly. The budding of progeny viruses that contain activated hemagglutinin-neuraminidase and fusion protein molecules in their outer coats causes the plasma membrane of NDV-infected cells to fuse with the plasma membrane of adjacent cells, leading to the production of large, inviable fused cells known as syncytia.[
The specific mechanism by which nonlytic NDV strains cause cell death in cancer cells has not been completely elucidated, but in Vero cells (derived from kidney epithelium) it was determined that NDV caused cell death by decreasing DNA content, increasing the ratio of Bax to Bcl-2, increasing p53 level, and increasing caspase expression, resulting in apoptosis.[
As indicated previously, both lytic strains and nonlytic strains have been investigated for their anticancer potential. In fact, the major differences between the two strain types have been exploited to develop three different approaches to cancer therapy:
One proposed advantage of the first approach is that virus replication may allow the spread of cytotoxic viruses to every cancer cell in the body;[
The principal developers of the third approach have stated that whole cell vaccines can stimulate the immune system better than oncolysates, and that cells infected with a nonlytic strain of NDV will remain intact in the body long enough to generate these more effective immune responses.[
Either a patient's own cancer cells (i.e., autologous cells) or cells from another patient with the same type of cancer (i.e., allogeneic cells) can be used to make oncolysates and whole cell vaccines. It is important to note that immune system responses similar to those obtained with oncolysates and whole cell vaccines may occur in patients infected with a lytic strain of NDV and that these responses would be expected to contribute to any observed anticancer effect.
To conduct human studies with viruses, vaccines, or other biological materials in the United States, researchers must file an Investigational New Drug (IND) application with the U.S. Food and Drug Administration (FDA). Biological materials and drugs have been held to similar safety and effectiveness standards since 1972. In an IND application, researchers must provide safety and toxicity data from laboratory and animal studies to justify the dose, the route, and the schedule of administration to be used in the proposed clinical studies. Among the safety issues to be addressed, researchers must demonstrate an absence of harmful contaminants. Most human studies of NDV as an anticancer agent have taken place outside the United States; therefore, they have not required an IND. At present, at least one group of U.S. investigators has filed an IND application to study NDV as an anticancer treatment.[
The NDV strains that have been evaluated most widely for the treatment of cancer are 73-T, MTH-68, and Ulster.[
In animal studies, NDV infection has been accomplished by intratumoral, intraperitoneal, intravenous, intramuscular, or subcutaneous injection.[
In human studies, NDV oncolysates have been administered by subcutaneous [
NDV Strain | Strain Type | Formulation | Suggested Mechanism(s) of Action | Reference Citation(s) |
---|---|---|---|---|
a Refer to text and theNCI Dictionary of Cancer Termsfor additional information and definition of terms. | ||||
b Oncolysates are prepared from virus-infected cancer cells; they consist primarily of cellmembranefragments and contain virus proteins and cancer cell proteins. | ||||
73-T | Lytic | Infectious virus | Cancer cells killed by virus; stimulation of immune system | [ |
73-T | Lytic | Oncolysate vaccineb | Stimulation of immune system | [ |
Ulster | Nonlytic | Infected tumor-cell vaccine | Stimulation of immune system | [ |
MTH-68 | Lytic | Infectious virus | Cancer cells killed by virus; stimulation of immune system | [ |
Italien | Lytic | Oncolysate vaccine/infectious virus | Stimulation of immune system; cancer cells killed by virus | [ |
Hickman | Lytic | Infectious virus | Cancer cells killed by virus; stimulation of immune system | [ |
PV701 | Lytic | Infectious virus | Cancer cells killed by virus; stimulation of immune system | [ |
HUJ | Lytic | Infectious virus | Cancer cells killed by virus; stimulation of immune system | [ |
La Sota | Not specified | Infected tumor cell vaccine | Not specified | [ |
References:
The first published report to establish a link between infection with a virus and the regression of cancer appeared in 1912.[
As indicated previously (refer to the General Information section of this summary for more information), cells infected with NDV can be killed directly by the virus or indirectly through an immune system response to the infection. The immune system uses a variety of approaches to kill virus-infected cells, including attack by cytotoxic cells (i.e., natural killer cells and/or cytotoxic T cells); attack by antivirus antibodies, which are made by B cells; and the release of cytokines.[
Cytokines can be directly cytotoxic to virus-infected cells (e.g., tumor necrosis factor [TNF] -alpha).[
As also indicated previously (refer to the General Information section of this summary for more information), if the immune system is responding to virus-infected cancer cells (or fragments of cancer cells), then better recognition of tumor-specific antigens may occur, and an increased ability to kill uninfected cancer cells may be acquired.[
References:
Effects of Newcastle Disease Virus on Human Cancer Cells
The ability of Newcastle disease virus (NDV) to replicate efficiently in human cancer cells has been demonstrated in both laboratory studies and animal studies.[
Lytic strain 73-T has been shown to replicate efficiently in human tumor cells [
Lytic strain Roakin has been reported to kill human lymphoma B cells and T cells transformed in vitro from a Hodgkin lymphoma patient four to five times faster than it killed normal, resting human white blood cells.[
Lytic strain Italien (or Italian) has been shown to kill human squamous cell lung carcinoma, melanoma, breast carcinoma, and larynx carcinoma, but not cervical carcinoma, cells in vitro.[
Overall, these results suggest that the lytic strains of NDV replicate well in some types of normal cells and replicate poorly in some types of cancer cells. These data and the absence of serious illness in individuals infected with NDV [
Nonlytic NDV strain Ulster has also been shown to replicate efficiently in human cancer cells in vitro, including cells of the following types of human tumors:
This strain does not replicate efficiently in normal human white blood cells in vitro.[
The ability of lytic strains of NDV to kill human cancer cells in vivo has also been examined. In xenograft studies, human cancer cells were injected either subcutaneously or intradermally into athymic, nude mice (i.e., mice that do not reject tumor cells from other animals because they have a defective immune system), and tumors were allowed to form. NDV was injected directly into the tumors, and tumor growth and animal survival were monitored. Injection produced complete tumor regression in 75% to 100% of mice bearing human fibrosarcoma, neuroblastoma, or cervical carcinoma tumors.[
Intratumoral injection of strain Italien was associated with complete tumor regression in 100% of mice bearing human melanoma tumors. The growth of metastatic tumors in these animals was not affected, suggesting that the virus was unable to disseminate widely throughout the body.[
In the above-mentioned neuroblastoma xenograft study, strain 73-T replicated over time in tumor tissue but replicated poorly when injected into the thigh muscle of athymic, nude mice.[
In another nude mouse study, strain V4UPM inhibited the growth of some cell lines of subcutaneously injected human glioblastoma multiforme cells.[
In yet another nude mouse study, a single intraperitoneal injection of strain 73-T in mice bearing human neuroblastoma xenografts resulted in complete, durable tumor regressions in 9 of 12 (75%) of the treated mice.[
Athymic, nude mice make small numbers of T cells, and they produce interferons, natural killer cells, and macrophages.[
NDV and Cancer Immunotherapy
Other laboratory and animal studies have shown that NDV and NDV-infected cancer cells can stimulate a variety of immune system responses that are essential to the successful immunotherapy of cancer.[
Two of these in vitro studies demonstrated that infection of human immune cells with NDV causes the cells to produce and release cytokines interferon-alpha and tumor necrosis factor (TNF)-alpha.[
Some in vitro studies have shown that NDV-infected human cancer cells are better at activating human cytotoxic T cells, helper T cells, and natural killer cells than uninfected cancer cells.[
Laboratory studies have shown that the interaction between NDV-infected cancer cells and T cells can be improved if monoclonal antibodies that bind the hemagglutinin-neuraminidase protein on the cancer cells and either the CD3 protein or the CD28 protein on T cells (i.e., bispecific monoclonal antibodies) are also used.[
As noted above, animal cells and animal tumor models have also been used to explore the immunotherapy potential of NDV. ESb, a mouse model of metastatic T-cell lymphoma has been employed in most of this work;[
In one study,[
In another study,[
Other studies with NDV Ulster and the ESb tumor model support the idea that virus proteins inserted in the plasma membrane of NDV-infected cancer cells may help the immune system recognize tumor-specific antigens better, potentially leading to an increased ability to kill uninfected cancer cells and virus-infected cells.[
One factor that may influence the effectiveness of NDV/tumor cell vaccines is overall tumor burden. Results obtained with the B16 mouse melanoma model suggest that these vaccines are less effective in individuals with advanced metastatic disease.[
References:
The anticancer potential of Newcastle disease virus (NDV) has been investigated in clinical studies in the United States, Canada, China, Germany, and Hungary. These studies have evaluated the use of oncolysates,[
Immunotherapy With Oncolysates
The following information is summarized in Table 2 below.
The use of NDV oncolysates in patients with metastatic melanoma was evaluated in four clinical studies in the United States.[
In the phase I study,[
As indicated above, the researchers who conducted this phase I study also conducted two phase II studies. The phase II studies tested the ability of NDV oncolysates to delay the progression of melanoma from regional cancer to systemic disease.[
The first phase II study involved 32 patients, 5 of whom had been treated previously with other types of immunotherapy.[
In both studies, the patients were given subcutaneous injections of NDV oncolysates once a week for 4 weeks, beginning 4 to 8 weeks after surgery, followed by more subcutaneous injections given every 2 weeks until 1 year after surgery, and then continued subcutaneous injections given at intervals that increased gradually to every 3 months over the course of a 5-year period. From years 5 through 15 after surgery, some patients received additional oncolysate injections, which were given at intervals varying in length from 3 months to 6 months. Four of the patients in the first study were treated with both autologous and allogeneic vaccines, whereas the remaining patients in that study and all of the patients in the second study were treated with allogeneic vaccines only. Five years after surgery, 72% of the patients in the first study and 63% of the patients in the second study were reported to be alive and free of detectable melanoma.[
The fourth U.S. study of NDV oncolysates in patients with melanoma was also a phase II trial.[
In contrast to the evidence of benefit found in the other phase II trials, the absence of benefit for NDV oncolysates in this fourth clinical trial remains to be explained. It has been reported that different methods of oncolysate preparation were used by the two groups of investigators who conducted these studies.[
Two additional phase II studies of NDV oncolysates have been conducted in Germany. One study involved 208 patients with locally advanced renal cell carcinoma (i.e., large tumors and no regional lymph node metastasis or tumors of any size and 1 or 2 regional lymph nodes positive for cancer).[
In the advanced renal cell carcinoma study,[
The researchers who conducted this study concluded that the results demonstrated improved disease-free survival for the study subjects in comparison with survival data published in the scientific literature for similar patients who were treated with surgery alone.[
The same research group conducted a parallel investigation in which immune system responses to combination oncolysate and cytokine therapy were measured in 38 patients who had advanced renal cell carcinoma.[
The phase II study of NDV oncolysates in patients with metastatic breast or metastatic ovarian cancer was described by its investigators as a study of autologous, whole cell vaccines.[
In the study, 22 patients were vaccinated by intradermal injection at least 3 times during a 6- to 8-week period that began 2 weeks after surgery to remove malignant cells (either primary tumor cells or metastatic tumor cells). The patients also received intravenous injections of cyclophosphamide, high-dose recombinant interleukin-2, and autologous lymphocytes that had been simulated in vitro by treatment with interleukin-2. The cyclophosphamide was administered to block the activity of a class of T cells (i.e., suppressor T cells) that might weaken the desired immune responses. On average, the patients were followed for a period of 23 months from the time of surgery. Nine patients were reported to have either a complete response or a partial response after vaccine therapy. Five patients had stable disease, and eight had progressive disease. The average duration of response was 5 months, after which disease progression was again observed. Blood samples taken from the patients during therapy showed increases in the numbers of NK cells and increases in serum concentrations of the cytokines interferon-alpha and TNF-alpha, but these changes did not persist. No other immune system responses were detected. Because this was an uncontrolled study, it is unclear whether any of the observed clinical and/or immune system responses can be attributed to treatment with NDV oncolysates. Furthermore, because the lytic strain Italien was used in the study, the possibility that the observed tumor regressions were due, in part, to oncolysis cannot be ruled out.
Reference Citation(s) | Type of Study | Type of Cancer | No. of Patients: Enrolled; Treated; Controlc | Strongest Benefit Reportedd | Concurrent Therapye | Level of Evidence Scoref |
---|---|---|---|---|---|---|
No. = number. | ||||||
a Refer to text and theNCI Dictionary of Cancer Termsfor additional information and definition of terms. | ||||||
b Oncolysates are prepared from virus-infected cancer cells; they consist primarily of cellmembranefragments and contain virusproteinsand cancer cell proteins. | ||||||
c Number of patients treated plus number of patients control may not equal number of patients enrolled; number of patients enrolled = number of patients initially recruited/considered by the researchers who conducted a study; number of patients treated = number of enrolled patients who were given the treatment being studiedAND for whom results were reported; historical control subjects are not included in number of patients enrolled. | ||||||
d The strongest evidence reported that the treatment under study has anticancer activity or otherwise improves the well-being of cancer patients. | ||||||
e Chemotherapy, radiation therapy,hormonal therapy, or cytokine therapy given/allowed at the same time as oncolysate treatment. | ||||||
f For information about levels of evidence analysis and an explanation of the level of evidence scores, refer to Levels of Evidence for Human Studies of Integrative, Alternative, and Complementary Therapies. | ||||||
[ |
Phase II trial | Advanced melanoma | 32; 32; Historical controls | Improved overall survival | No | 3iiA |
[ |
Phase II trial | Advanced melanoma | 51; 51; Historical controls | Improved overall survival | No | 3iiA |
[ |
Phase II trial | Advanced melanoma | 24; 24; Historical controls | None | No | 3iiDi |
[ |
Phase II trial | Metastatic breast or ovarian | 22; 22; None | Complete/partial tumor response, 9 patients | Yes | 3iiDiii |
[ |
Phase II trial | Advanced renal cell | 208; 203; Historical controls | Improved disease-free survival | Yes | 3iiiDi |
[ |
Phase I trial | Advanced melanoma | 13; 13; None | Complete tumor response, 1 patient | Yes | 3iiiDii |
Immunotherapy With Whole Cell Vaccines
The following information is summarized in Table 3 below.
Most clinical studies of NDV-infected, whole cell vaccines that have been reported in scientific literature were conducted in Germany.[
Data from a 2004 pilot clinical trial of an NDV-modified autologous tumor vaccine in 20 patients with stage III or IV head and neck squamous cell carcinomas suggest that the vaccine strategy can stimulate human antitumor immune responses in a manner similar to those found in animal models and may significantly prolong 5-year survival rates in this patient population. The study demonstrated the feasibility and safety of the vaccine regimen, and no major side effects were observed in any of the patients.[
The use of NDV-infected, whole cell vaccines in patients with either locally advanced or metastatic colorectal carcinoma was examined in one phase I clinical trial and two phase II clinical trials.[
In the trial, NDV-infected, autologous whole cell vaccines were administered to patients by intradermal injection beginning 4 weeks after surgery to remove the primary tumor or the metastatic tumor. Each patient received a total of 5 vaccinations, 4 given at 10-day intervals and a final booster given approximately 23 weeks after surgery. One of the study reports [
The two phase II trials looked for evidence of therapeutic benefit in patients who had either metastatic colorectal carcinoma [
During 18 months of follow-up, 14 of the 23 (61%) patients in this trial had relapses of their cancer, compared with relapses in 20 of 23 (87%) historical control subjects who were treated with surgery alone by the same surgeons at the same hospital. Although this difference in disease-free survival was statistically significant, there was no statistically significant difference in overall survival between the study subjects and the historical control subjects. The researchers also reported that, in general, the patients who had the strongest immune system responses against uninfected autologous tumor cells after vaccination had the longest disease-free survival times. It should be noted, however, that the reporting of patient responses against uninfected autologous tumor cells in this trial was inconsistent.[
The phase II trial that involved patients with locally advanced colorectal carcinoma (i.e., large tumors and no regional lymph node metastasis or tumors of any size and regional lymph nodes that were positive for cancer) recruited 57 individuals.[
Two additional phase II studies investigated the use of NDV-infected, autologous tumor cell vaccines in patients who had either ovarian cancer or renal cell cancer.[
The phase II trial of NDV-infected, autologous tumor cell vaccines in patients with renal cell cancer enrolled 40 individuals whose disease had spread from the kidney to at least 1 other organ.[
A fifth phase II clinical trial tested NDV-infected, autologous tumor cell vaccines in 43 patients who had various advanced cancers (16 ovarian, 22 breast, 1 cervical, 1 vaginal, 1 lung, and 1 chondrosarcoma) that had not responded to previous treatment.[
One additional clinical study evaluated the effect of vaccine quality on the survival of patients who were treated with NDV-infected, autologous tumor cells.[
Overall survival 4 years after surgery was estimated to be 96% for the patients with early breast cancer who had received a high-quality vaccine (n = 32), compared with an overall survival of 68% for those who had received a low-quality vaccine (n = 31). For the patients with metastatic breast cancer, the median survival time was estimated to be 1.75 years from the start of immunotherapy for those who had received a high-quality vaccine (n = 13), compared with a median survival time of 0.75 years for those who had received a low-quality vaccine (n = 14) (median follow-up time = 1.4 years). For patients with metastatic ovarian cancer, the median survival time was estimated to be 1.16 years from the start of immunotherapy for those who had received a high-quality vaccine (n = 18), compared with a median survival time of 0.84 years for those who had received a low-quality vaccine (n = 13) (median follow-up time = 1.23 years). The only survival difference that was statistically significant was the one for the patients who had early breast cancer. The retrospective nature of this study and the small numbers of patients in each treatment group should be viewed as major weaknesses.
In two of the above-mentioned studies, the phase I colorectal cancer study [
Reference Citation(s) | Type of Study | Type of Cancer | No. of Patients: Enrolled; Treated; Controlb | Strongest Benefit Reportedc | Concurrent Therapyd | Level of Evidence Scoree |
---|---|---|---|---|---|---|
No. = number; wk = week. | ||||||
a Refer to text and theNCI Dictionary of Cancer Termsfor additional information and definition of terms. | ||||||
b Number of patients treated plus number of patients control may not equal number of patients enrolled; number of patients enrolled = number of patients initially recruited/considered by the researchers who conducted a study; number of patients treated = number of enrolled patients who were given the treatment being studiedAND for whom results were reported; historical control subjects are not included in number of patients enrolled. | ||||||
c The strongest evidence reported that the treatment under study has anticancer activity or otherwise improves the well-being of cancer patients. | ||||||
d Chemotherapy, radiation therapy, hormonal therapy, or cytokine therapy given/allowed at the same time as vaccine therapy. | ||||||
e For information about levels of evidence analysis and an explanation of the level of evidence scores, refer to Levels of Evidence for Human Studies of Integrative, Alternative, and Complementary Therapies. | ||||||
f Only 48 patients were treated with NDV-infected tumor cell vaccines; the remaining patients were treated with another type of vaccine. | ||||||
g The patients were divided into groups that received a high-quality vaccine or a low-quality vaccine; the low-quality vaccine groups served as the controls; 32, 13, and 18 patients with early breast cancer, metastatic breast cancer, and metastatic ovarian cancer, respectively, received high-quality vaccines; the corresponding low-quality vaccine groups contained 31,14, and 13 patients. | ||||||
h There were 39 evaluable patients in this study, but findings were reported for only 24 patients. | ||||||
i Article does not provide enough information. | ||||||
[ |
Phase II/III (adjuvant setting) | Melanoma | 29; 21; 8 | No advantage of vaccine for disease free survival or overall survival | None | 1iA |
[ |
Phase III (adjuvant setting) | Colorectal with liver metastases | 51; 25; 26 | Planned subgroup analysis, overall and disease free survival advantages in the colon of cancer patients | Protocol therapy was given after complete surgical resection of primary tumor and liver metastases | 1iiA |
[ |
Phase II | Glioblastoma | 35; 23; 87 (concurrent controls identified from within same hospital) | Median progression-free survival of vaccinated patients was 40 wk (vs. 26 wk in controls; log-rank test,P = .024), median OS of vaccinated patients was 100 wk (vs. 49 wk in controls; log-rank test,P< .001) | Protocol therapy after surgical debulking of tumor followed by radiation therapy | 2A |
[ |
Phase II trial | Metastatic colorectal | 23; 23; Historical controls | Improved disease-free survival | No | 3iiA |
[ |
Phase II trial | Ovarian | 82; 24h; None | Improved disease-free survival | Yes | 3iiDi |
[ |
Phase II trial | Advanced colorectal | 57; 48f; Historical controls | Improved overall survival | No | 3iiiA |
[ |
Retrospective analysis | Early breast | 63; 63; Internal controlsg | Improved overall survival | Yes | 3iiiA |
[ |
Phase II trial | Metastatic renal cell | 40; 40; Historical controls | Improved overall survival, 11 patients with complete/partial responses | Yes | 3iiiA |
[ |
Phase II trial | Various advanced | 43; 31; None | Complete tumor response, 1 patient | Yes | 3iiiDiii |
[ |
Phase II | Gastrointestinal tumors, stage IV | 25; 25; 0 | 1 Complete response, 5 partial responses, overall response rate = 24% | None described | 3iiiDiii |
[ |
Phase III | Colorectal | 567; 310; 257 | Higher mean and median survival for vaccination group compared to the resection group alone | None described | None describedi |
Infection of Patients With NDV (Including Strain MTH-68)
The following information is summarized in Table 4 below.
To date, most research into the treatment of human cancer by infection of patients with NDV has been conducted in Hungary.[
The five patients described in the case report and the small case series were reported to have had either a complete remission or a partial remission following NDV therapy.[
In the phase II trial,[
This phase II trial had a number of weaknesses that could have influenced its outcome. The most important weakness is the fact that the patients were not randomly assigned to the two treatment groups. This lack of randomization raises the possibility of selection bias. In this regard, it is noteworthy that a larger percentage of patients in the NDV treatment group than in the placebo group received conventional therapy within the 3 months preceding the initiation of NDV therapy (82% vs. 58%).[
In a phase I trial that was conducted in the United States, another lytic NDV strain, PV701, was tested in patients with various advanced cancers.[
The researchers found that the use of lower initial doses of virus allowed the administration of higher subsequent doses. A complete response was reported for one patient, and partial tumor regression was observed in eight patients. Thirteen patients had stable disease for periods of time that lasted from 4 months to more than 30 months. Five patients died during the trial: four due to progressive disease and one due, possibly, to a treatment-related complication (refer to the Adverse Effects section of this summary for more information). Several patients experienced significant adverse side effects from NDV treatment, including fever, fatigue, dehydration, low blood pressure, shortness of breath, and hypoxia. Some patients who experienced these adverse effects required hospitalization. The researchers who conducted this trial have indicated that additional clinical studies are under way.
A major concern about the effectiveness of treating cancer patients by repeated administration of a lytic strain of NDV is the possibility that the immune system will produce virus-neutralizing antibodies. Virus-neutralizing antibodies would prevent NDV from reaching and infecting malignant cells, thereby blocking oncolysis. Impairment of NDV infection would also limit the ability of cytotoxic T cells that target virus antigens to kill virus-infected cancer cells. In addition, limiting the infection of cancer cells would lessen the likelihood that the immune system would become trained to better recognize tumor-specific antigens. The Hungarian investigators have shown that anti-NDV antibodies are produced in MTH-68-treated patients,[
Reference Citation(s) | Type of Study | NDV Strain | Type of Cancer | No. of Patients: Enrolled; Treated; Controlb | Strongest Benefit Reportedc | Concurrent Therapyd | Level of Evidence Scoree |
---|---|---|---|---|---|---|---|
mo = month; No. = number. | |||||||
a Refer to text and theNCI Dictionary of Cancer Termsfor additional information and definition of terms. | |||||||
b Number of patients treated plus number of patients control may not equal number of patients enrolled; number of patients enrolled = number of patients initially recruited/considered by the researchers who conducted a study; number of patients treated = number of patients who were given the treatment being studiedAND for whom results were reported; historical control subjects are not included in number of patients enrolled. | |||||||
c The strongest evidence reported that the treatment under study has anticancer activity or otherwise improves the well being of cancer patients. | |||||||
d Chemotherapy, radiation therapy, hormonal therapy, or cytokine therapy given/allowed at the same time as virus treatment. | |||||||
e For information about levels of evidence analysis and an explanation of the level of evidence scores, refer to Levels of Evidence for Human Studies of Integrative, Alternative, and Complementary Therapies. | |||||||
f This patient was treated with chemotherapy and five other types of virus in addition to NDV. | |||||||
[ |
Phase II trial | MTH-68 | Various advanced | 59; 33; 26, placebo | Improved overall survival | No | 2A |
[ |
Phase I trial | PV701 | Various advanced | 79; 79; None | Partial tumor regression, 8 patients | Unknown | 3iiiDiii |
[ |
Phase I/II | HUJ | Glioblastoma multiforme, recurrent | 14 (phase I–6; phase II–8); 11 (phase I–6, phase II–5); 0 | 1 transient (3 mo) complete response, all other patients had progressive disease | None | 3iiiDiii |
[ |
Case series | MTH-68 | Various advanced | 4; 4; None | Complete tumor regression, 2 patients | Yes | 4 |
[ |
Selected case series | MTH-68/H | Gliomas, high-grade | 4; 4; 0 | Radiographically documented responses and long survival with improved symptomatology | Various | 4Diii |
[ |
Phase I | PV701 | Various | 16; 16; 0 | Improved patient tolerability with two-step desensitization | None | N/A |
[ |
Case report | MTH-68/H | Anaplastic astrocytoma | 1; 1; 0 | Partial response | Valproic acid | N/A |
[ |
Case report | 73-T | Advanced cervical | 1; 1; None | Partial tumor regression | No | None |
[ |
Anecdotal report | MTH-68 | Various metastatic | 3; 3; None | Tumor regression | Unknown | None |
[ |
Case report | MTH-68 | Glioblastoma multiforme | 1; 1; None | Partial tumor regression | Yes | None |
[ |
Case report | Hickman | Acute myeloid leukemia | 1; 1; None | Partial response | Yesf | None |
Current Clinical Trials
Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.
References:
The side effects associated with exposure to Newcastle disease virus (NDV) have generally been described as mild to moderate in severity. As noted previously (refer to the General Information section of this summary for more information), NDV has been reported to cause mild flu-like symptoms, conjunctivitis, and laryngitis in humans. [
The most commonly reported side effect after treatment of cancer patients with the virus alone is fever, which usually subsides within 24 hours.[
Mild headache, mild fever on the day of vaccination, and itching, swelling, and erythema at injection sites are the most commonly reported side effects following injection of NDV-infected whole cell vaccines.[
The only adverse effect associated with administration of NDV oncolysate vaccines is inflammation at injection sites.[
Most of the flu-like symptoms, fever, and edema observed in studies in which cytokines were combined with NDV oncolysates or whole cell vaccines have been attributed to treatment with interleukin-2.[
References:
In view of the evidence accumulated, no conclusions can be drawn about the effectiveness of using Newcastle disease virus in the treatment of cancer. Most reported clinical studies have involved few patients, and historical control subjects rather than actual control groups have often been used for outcome comparisons. Poor descriptions of study design and incomplete reporting of clinical data have hindered evaluation of many of the reported findings. However, while most studies are small and lack adequate controls, the number of studies suggesting a potential clinical value warrants further attention.
Separate levels of evidence scores are assigned to qualifying human studies on the basis of statistical strength of the study design and scientific strength of the treatment outcomes (i.e., endpoints) measured. The resulting two scores are then combined to produce an overall score. For additional information about levels of evidence analysis, refer to Levels of Evidence for Human Studies of Integrative, Alternative, and Complementary Therapies.
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
Editorial changes were made to this summary.
This summary is written and maintained by the PDQ Integrative, Alternative, and Complementary Therapies Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® - NCI's Comprehensive Cancer Database pages.
Purpose of This Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the use of Newcastle disease virus in the treatment of people with cancer. It is intended as a resource to inform and assist clinicians in the care of their patients. It does not provide formal guidelines or recommendations for making health care decisions.
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Levels of Evidence
Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Integrative, Alternative, and Complementary Therapies Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.
Permission to Use This Summary
PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as "NCI's PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary]."
The preferred citation for this PDQ summary is:
PDQ® Integrative, Alternative, and Complementary Therapies Editorial Board. PDQ Newcastle Disease Virus. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/about-cancer/treatment/cam/hp/ndv-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389195]
Images in this summary are used with permission of the author(s), artist, and/or publisher for use within the PDQ summaries only. Permission to use images outside the context of PDQ information must be obtained from the owner(s) and cannot be granted by the National Cancer Institute. Information about using the illustrations in this summary, along with many other cancer-related images, is available in Visuals Online, a collection of over 2,000 scientific images.
Disclaimer
The information in these summaries should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on Cancer.gov on the Managing Cancer Care page.
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Last Revised: 2018-08-22
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