NDV is a paramyxovirus that causes Newcastle disease in a wide variety of birds (most notably, in chickens).[1-3] This often fatal disease is characterized by inflammation of respiratory tract and of either the brain or the gastrointestinal tract.[1,2,4,5] NDV can also infect humans, but, in humans, it is generally not very virulent, causing only mild flu-like symptoms or conjunctivitis and/or laryngitis.[1,6-14] The perception that NDV can replicate up to 10,000 times better in human cancer cells than in most normal human cells [2,6-10,12,13,15-23] has prompted much interest in this virus as a potential anticancer agent. This phenomenon is apparently caused by defects in intracellular antiviral defenses of some cancer cells.[24-26] NDV was historically considered a CAM approach, but in recent years it has been extensively studied by the conventional medical community. Also, genetically engineered NDV strains are being developed and studied for their anticancer activity.
The genetic material of NDV is RNA rather than DNA.[1,3,13,18,23,28-31] As with other types of viruses, essentially all of NDV’s replication cycle takes place inside infected cells, which are also known as host cells.[13,18,30,32] During a replication cycle, new virus proteins and copies of the NDV genetic material (i.e., genome) are made in the host cell’s cytoplasm. NDV is also an enveloped virus, which means that progeny virus particles are released from infected cells by budding off from them.[18,30,33] In this process, single copies of the NDV genome become wrapped in an outer coat (i.e., an envelope) that is made from a small piece of the host cell’s plasma membrane. Generally, the NDV outer coat contains only virus proteins that have been specifically inserted into the host cell's plasma membrane;[18,28,32,33] however, some host cell proteins may be included as well.[34,35] Two specific virus proteins, hemagglutinin-neuraminidase and the fusion protein, are the main NDV proteins found in the outer coat of isolated virus particles.[3,18,28,30]
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,[12,13,15-20,36] and viruses of both strain types have been investigated as potential anticancer agents. One major difference between lytic strains and nonlytic strains is that lytic strains are able to make infectious progeny virus particles in human cells, whereas nonlytic strains are not.[13,18,28-30,37] This difference is due to the ability of lytic strains to produce activated hemagglutinin-neuraminidase and fusion protein molecules in the outer coat of progeny viruses in human cells. The progeny virus particles made by nonlytic strains contain inactive versions of these molecules. Activated hemagglutinin-neuraminidase and fusion protein molecules are required for NDV to enter a cell to replicate. Initial binding of NDV to a host cell takes place through the interaction of hemagglutinin-neuraminidase molecules in the virus coat with sialic-acid –containing molecules (i.e., gangliosides) on the surface of the cell. It is important to note, however, that nonlytic strains of NDV can make infectious progeny viruses in some types of nonhuman cells (e.g., chicken embryo cells), thereby allowing these strains to be maintained.[13,18,28,29,36]
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.[12,13,18,30] The more efficiently a lytic strain can replicate inside a host cell, the more quickly it can kill that cell. The preferential killing of cancer cells by a lytic virus is known as oncolysis; thus, lytic strains of NDV are also called oncolytic strains. Nonlytic strains of NDV kill infected cells more slowly, with death apparently the result of viral disruption of normal host cell metabolism.[36,38]
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.[39-41]
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:
- The infection of cancer patients with a lytic strain of NDV.
- The use of oncolysates, i.e., preparations containing plasma membrane fragments from NDV-infected cancer calls, as anticancer vaccines.
- The use of intact cancer cells infected with a nonlytic strain of NDV as whole cell vaccines.
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;[8,34] however, the production of virus-neutralizing antibodies by the immune system might limit this possibility.[6,8,13,30,40] The rationale for the second and third approaches is that tumor-specific antigens (i.e., proteins or other molecules that are generally located in the plasma membrane of cancer cells and that are either unique to cancer cells or much more abundant in them) may be better recognized by the immune system if they are associated with virus antigens (i.e., virus proteins that have been inserted into the plasma membrane of host cells).[8,12,13,28,32,34,42-48] If this enhanced recognition takes place, then it may increase the chance that cancer cells, whether they are virus infected or not, will be recognized as foreign by the immune system and be destroyed.[8,12,28,47,48]
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.[18,28,29,36-38,43,46,49-51] It should be noted that the cancer cells used in the third approach are treated with enough gamma radiation to prevent further cell division, but not enough to cause cell death, either before or after they are infected with the nonlytic virus.[49,50,52-58,13] This precaution ensures that patients are not given a vaccine that contains actively proliferating cancer cells.
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. It should be noted that the FDA has not approved the use of NDV to treat any medical condition.
The NDV strains that have been evaluated most widely for the treatment of cancer are 73-T, MTH-68, and Ulster.[1,6,11,22,42,45,49-58,60-74] Strain 73-T is lytic, and Ulster is nonlytic. Strain MTH-68 has not been classified, but it is assumed to be lytic.[1,6,66,75,22,76,77] All three strains have shown little or no evidence of neurotropism (i.e., an ability to replicate efficiently in normal nerve cells or normal neural tissue).
In animal studies, NDV infection has been accomplished by intratumoral, intraperitoneal, intravenous, intramuscular, or subcutaneous injection.[9,10,12,23,28,36,36,43,78] NDV-infected, whole cell vaccines have been given to animals by intraperitoneal, intradermal, or subcutaneous injection,or by a combination of subcutaneous and intramuscular injection.[36,43,79]
In human studies, NDV oncolysates have been administered by subcutaneous [11,42,45,60,63,65,67-70] or intradermal [62,64] injection. NDV-infected, whole cell vaccines have been administered by intradermal injection only.[49,50,52-58,71-73] In cases where patients have been infected with a lytic strain of NDV, intratumoral, intravenous,[1,59,66,80] or intramuscular  injection has been used, as have inhalation [1,6] and direct injection into the colon (i.e., via a colostomy opening). In some instances, cytokine treatment has been combined with NDV therapy.[45,52,53,56,62,64,65,70]Table 1. Strains of NDV Tested in Human/Clinical Cancer Studiesa
|NDV Strain||Strain Type||Formulation||Suggested Mechanism(s) of Action||Reference Citation(s)|
|73-T||Lytic||Infectious virus||Cancer cells killed by virus; stimulation of immune system|||
|73-T||Lytic||Oncolysate vaccineb||Stimulation of immune system||[11,42,45,60,63,65,67-70]|
|Ulster||Nonlytic||Infected tumor-cell vaccine||Stimulation of immune system||[49,50,52-58,71-73]|
|MTH-68||Lytic||Infectious virus||Cancer cells killed by virus; stimulation of immune system||[1,6,61,66]|
|Italien||Lytic||Oncolysate vaccine/infectious virus||Stimulation of immune system; cancer cells killed by virus||[62,64]|
|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|||
|aRefer to text and the NCI Dictionary of Cancer Terms for additional information and definition of terms.|
|bOncolysates are prepared from virus-infected cancer cells; they consist primarily of cell membrane fragments and contain virus proteins and cancer cell proteins.|
- Csatary LK, Moss RW, Beuth J, et al.: Beneficial treatment of patients with advanced cancer using a Newcastle disease virus vaccine (MTH-68/H). Anticancer Res 19 (1B): 635-8, 1999 Jan-Feb. [PUBMED Abstract]
- Nelson NJ: Scientific interest in Newcastle disease virus is reviving. J Natl Cancer Inst 91 (20): 1708-10, 1999. [PUBMED Abstract]
- Seal BS, King DJ, Sellers HS: The avian response to Newcastle disease virus. Dev Comp Immunol 24 (2-3): 257-68, 2000 Mar-Apr. [PUBMED Abstract]
- Alexander DJ, Allan WH: Newcastle disease virus pathotypes. Avian Pathol 3 (4): 269-78, 1974.
- Hanson RP: The reemergence of Newcastle disease. Adv Vet Sci Comp Med 18 (0): 213-29, 1974. [PUBMED Abstract]
- Csatary LK, Eckhardt S, Bukosza I, et al.: Attenuated veterinary virus vaccine for the treatment of cancer. Cancer Detect Prev 17 (6): 619-27, 1993. [PUBMED Abstract]
- Kenney S, Pagano JS: Viruses as oncolytic agents: a new age for "therapeutic" viruses? J Natl Cancer Inst 86 (16): 1185-6, 1994. [PUBMED Abstract]
- Kirn DH, McCormick F: Replicating viruses as selective cancer therapeutics. Mol Med Today 2 (12): 519-27, 1996. [PUBMED Abstract]
- Lorence RM, Reichard KW, Katubig BB, et al.: Complete regression of human neuroblastoma xenografts in athymic mice after local Newcastle disease virus therapy. J Natl Cancer Inst 86 (16): 1228-33, 1994. [PUBMED Abstract]
- Lorence RM, Katubig BB, Reichard KW, et al.: Complete regression of human fibrosarcoma xenografts after local Newcastle disease virus therapy. Cancer Res 54 (23): 6017-21, 1994. [PUBMED Abstract]
- Batliwalla FM, Bateman BA, Serrano D, et al.: A 15-year follow-up of AJCC stage III malignant melanoma patients treated postsurgically with Newcastle disease virus (NDV) oncolysate and determination of alterations in the CD8 T cell repertoire. Mol Med 4 (12): 783-94, 1998. [PUBMED Abstract]
- Reichard KW, Lorence RM, Cascino CJ, et al.: Newcastle disease virus selectively kills human tumor cells. J Surg Res 52 (5): 448-53, 1992. [PUBMED Abstract]
- Schirrmacher V, Ahlert T, Pröbstle T, et al.: Immunization with virus-modified tumor cells. Semin Oncol 25 (6): 677-96, 1998. [PUBMED Abstract]
- Moss RW: Alternative pharmacological and biological treatments for cancer: ten promising approaches. J Naturopathic Med 6 (1): 23-32, 1996.
- Bar-Eli N, Giloh H, Schlesinger M, et al.: Preferential cytotoxic effect of Newcastle disease virus on lymphoma cells. J Cancer Res Clin Oncol 122 (7): 409-15, 1996. [PUBMED Abstract]
- Tzadok-David Y, Metzkin-Eizenberg M, Zakay-Rones Z: The effect of a mesogenic and a lentogenic Newcastle disease virus strain on Burkitt lymphoma Daudi cells. J Cancer Res Clin Oncol 121 (3): 169-74, 1995. [PUBMED Abstract]
- Lorence RM, Rood PA, Kelley KW: Newcastle disease virus as an antineoplastic agent: induction of tumor necrosis factor-alpha and augmentation of its cytotoxicity. J Natl Cancer Inst 80 (16): 1305-12, 1988. [PUBMED Abstract]
- Schirrmacher V, Haas C, Bonifer R, et al.: Human tumor cell modification by virus infection: an efficient and safe way to produce cancer vaccine with pleiotropic immune stimulatory properties when using Newcastle disease virus. Gene Ther 6 (1): 63-73, 1999. [PUBMED Abstract]
- Zorn U, Dallmann I, Grosse J, et al.: Induction of cytokines and cytotoxicity against tumor cells by Newcastle disease virus. Cancer Biother 9 (3): 225-35, 1994 Fall. [PUBMED Abstract]
- Cassel WA, Garrett RE: Newcastle disease virus as an antineoplastic agent. Cancer 18 (7): 863-8, 1965.
- Reichard KW, Lorence RM, Katubig BB, et al.: Retinoic acid enhances killing of neuroblastoma cells by Newcastle disease virus. J Pediatr Surg 28 (10): 1221-5; discussion 1225-6, 1993. [PUBMED Abstract]
- Nemunaitis J: Oncolytic viruses yesterday and today. J Oncol Manag 8 (5): 14-24, 1999.
- Phuangsab A, Lorence RM, Reichard KW, et al.: Newcastle disease virus therapy of human tumor xenografts: antitumor effects of local or systemic administration. Cancer Lett 172 (1): 27-36, 2001. [PUBMED Abstract]
- Krishnamurthy S, Takimoto T, Scroggs RA, et al.: Differentially regulated interferon response determines the outcome of Newcastle disease virus infection in normal and tumor cell lines. J Virol 80 (11): 5145-55, 2006. [PUBMED Abstract]
- Fiola C, Peeters B, Fournier P, et al.: Tumor selective replication of Newcastle disease virus: association with defects of tumor cells in antiviral defence. Int J Cancer 119 (2): 328-38, 2006. [PUBMED Abstract]
- Aoki K, Oh-hira M, Hoshino M, et al.: Isolation and characterization of a novel mutant mouse cell line resistant to Newcastle disease virus: constitutive interferon production and enhanced interferon sensitivity. Arch Virol 139 (3-4): 337-50, 1994. [PUBMED Abstract]
- Vigil A, Park MS, Martinez O, et al.: Use of reverse genetics to enhance the oncolytic properties of Newcastle disease virus. Cancer Res 67 (17): 8285-92, 2007. [PUBMED Abstract]
- Schirrmacher V, Ahlert T, Heicappell R, et al.: Successful application of non-oncogenic viruses for antimetastatic cancer immunotherapy. Cancer Rev 5: 19-49, 1986.
- Schirrmacher V, Haas C, Bonifer R, et al.: Virus potentiation of tumor vaccine T-cell stimulatory capacity requires cell surface binding but not infection. Clin Cancer Res 3 (7): 1135-48, 1997. [PUBMED Abstract]
- Sinkovics JG, Horvath JC: Newcastle disease virus (NDV): brief history of its oncolytic strains. J Clin Virol 16 (1): 1-15, 2000. [PUBMED Abstract]
- Haas C, Herold-Mende C, Gerhards R, et al.: An effective strategy of human tumor vaccine modification by coupling bispecific costimulatory molecules. Cancer Gene Ther 6 (3): 254-62, 1999 May-Jun. [PUBMED Abstract]
- Haas C, Ertel C, Gerhards R, et al.: Introduction of adhesive and costimulatory immune functions into tumor cells by infection with Newcastle Disease Virus. Int J Oncol 13 (6): 1105-15, 1998. [PUBMED Abstract]
- Eaton MD, Heller JA, Scala AR: Enhancement of lymphoma cell immunogenicity by infection with nononcogenic virus. Cancer Res 33 (12): 3293-8, 1973. [PUBMED Abstract]
- Webb HE, Smith CE: Viruses in the treatment of cancer. Lancet 1 (7658): 1206-8, 1970. [PUBMED Abstract]
- Beverley PC, Lowenthal RM, Tyrrell DA: Immune responses in mice to tumour challenge after immunization with Newcastle disease virus-infected or x-irradiated tumour cells or cell fractions. Int J Cancer 11 (1): 212-23, 1973. [PUBMED Abstract]
- Schirrmacher V, Griesbach A, Ahlert T: Antitumor effects of Newcastle Disease Virus in vivo: local versus systemic effects. Int J Oncol 18 (5): 945-52, 2001. [PUBMED Abstract]
- Ahlert T, Schirrmacher V: Isolation of a human melanoma adapted Newcastle disease virus mutant with highly selective replication patterns. Cancer Res 50 (18): 5962-8, 1990. [PUBMED Abstract]
- Schirrmacher V, Jurianz K, Roth C, et al.: Tumor stimulator cell modification by infection with Newcastle Disease Virus: analysis of effects and mechanism in MLTC-CML cultures. Int J Oncol 14 (2): 205-15, 1999. [PUBMED Abstract]
- Ravindra PV, Tiwari AK, Ratta B, et al.: Newcastle disease virus-induced cytopathic effect in infected cells is caused by apoptosis. Virus Res 141 (1): 13-20, 2009. [PUBMED Abstract]
- Morse MA: Virus-based therapies for colon cancer. Expert Opin Biol Ther 5 (12): 1627-33, 2005. [PUBMED Abstract]
- Liu TC, Kirn D: Systemic efficacy with oncolytic virus therapeutics: clinical proof-of-concept and future directions. Cancer Res 67 (2): 429-32, 2007. [PUBMED Abstract]
- Cassel WA, Murray DR: A ten-year follow-up on stage II malignant melanoma patients treated postsurgically with Newcastle disease virus oncolysate. Med Oncol Tumor Pharmacother 9 (4): 169-71, 1992. [PUBMED Abstract]
- Heicappell R, Schirrmacher V, von Hoegen P, et al.: Prevention of metastatic spread by postoperative immunotherapy with virally modified autologous tumor cells. I. Parameters for optimal therapeutic effects. Int J Cancer 37 (4): 569-77, 1986. [PUBMED Abstract]
- Shoham J, Hirsch R, Zakay-Rones Z, et al.: Augmentation of tumor cell immunogenicity by viruses--an approach to specific immunotherapy of cancer. Nat Immun Cell Growth Regul 9 (3): 165-72, 1990. [PUBMED Abstract]
- Zorn U, Duensing S, Langkopf F, et al.: Active specific immunotherapy of renal cell carcinoma: cellular and humoral immune responses. Cancer Biother Radiopharm 12 (3): 157-65, 1997. [PUBMED Abstract]
- Plaksin D, Porgador A, Vadai E, et al.: Effective anti-metastatic melanoma vaccination with tumor cells transfected with MHC genes and/or infected with Newcastle disease virus (NDV). Int J Cancer 59 (6): 796-801, 1994. [PUBMED Abstract]
- Bier H, Armonat G, Bier J, et al.: Postoperative active-specific immunotherapy of lymph node micrometastasis in a guinea pig tumor model. ORL J Otorhinolaryngol Relat Spec 51 (4): 197-205, 1989. [PUBMED Abstract]
- DeVita VT Jr, Hellman S, Rosenberg SA, eds.: Cancer: Principles and Practice of Oncology. 5th ed. Philadelphia, Pa: Lippincott-Raven Publishers, 1997.
- Liebrich W, Schlag P, Manasterski M, et al.: In vitro and clinical characterisation of a Newcastle disease virus-modified autologous tumour cell vaccine for treatment of colorectal cancer patients. Eur J Cancer 27 (6): 703-10, 1991. [PUBMED Abstract]
- Ockert D, Schirrmacher V, Beck N, et al.: Newcastle disease virus-infected intact autologous tumor cell vaccine for adjuvant active specific immunotherapy of resected colorectal carcinoma. Clin Cancer Res 2 (1): 21-8, 1996. [PUBMED Abstract]
- Schirrmacher V: Active specific immunotherapy: a new modality of cancer treatment involving the patient's own immune system. Onkologie 16 (5): 290-6, 1993.
- Ahlert T, Sauerbrei W, Bastert G, et al.: Tumor-cell number and viability as quality and efficacy parameters of autologous virus-modified cancer vaccines in patients with breast or ovarian cancer. J Clin Oncol 15 (4): 1354-66, 1997. [PUBMED Abstract]
- Ahlert T: Tumor cell vaccination and IL-2 therapy. Hybridoma 12 (5): 549-52, 1993. [PUBMED Abstract]
- Bohle W, Schlag P, Liebrich W, et al.: Postoperative active specific immunization in colorectal cancer patients with virus-modified autologous tumor-cell vaccine. First clinical results with tumor-cell vaccines modified with live but avirulent Newcastle disease virus. Cancer 66 (7): 1517-23, 1990. [PUBMED Abstract]
- Lehner B, Schlag P, Liebrich W, et al.: Postoperative active specific immunization in curatively resected colorectal cancer patients with a virus-modified autologous tumor cell vaccine. Cancer Immunol Immunother 32 (3): 173-8, 1990. [PUBMED Abstract]
- Pomer S, Schirrmacher V, Thiele R, et al.: Tumor response and 4 year survival-data of patients with advanced renal-cell carcinoma treated with autologous tumor vaccine and subcutaneous R-IL-2 and IFN-alpha(2b). Int J Oncol 6 (5): 947-54, 1995. [PUBMED Abstract]
- Schlag P, Manasterski M, Gerneth T, et al.: Active specific immunotherapy with Newcastle-disease-virus-modified autologous tumor cells following resection of liver metastases in colorectal cancer. First evaluation of clinical response of a phase II-trial. Cancer Immunol Immunother 35 (5): 325-30, 1992. [PUBMED Abstract]
- Möbus V, Horn S, Stöck M, et al.: Tumor cell vaccination for gynecological tumors. Hybridoma 12 (5): 543-7, 1993. [PUBMED Abstract]
- Pecora AL, Rizvi N, Cohen GI, et al.: Phase I trial of intravenous administration of PV701, an oncolytic virus, in patients with advanced solid cancers. J Clin Oncol 20 (9): 2251-66, 2002. [PUBMED Abstract]
- Cassel WA, Murray DR, Phillips HS: A phase II study on the postsurgical management of Stage II malignant melanoma with a Newcastle disease virus oncolysate. Cancer 52 (5): 856-60, 1983. [PUBMED Abstract]
- Csatary LK: Viruses in the treatment of cancer. Lancet 2 (7728): 825, 1971. [PUBMED Abstract]
- Mallmann P: Autologous tumor-cell vaccination and lymphokine-activated tumor-infiltrating lymphocytes (LAK-TIL). Hybridoma 12 (5): 559-66, 1993. [PUBMED Abstract]
- Plager C, Bowen JM, Fenoglio C, et al.: Adjuvant immunotherapy of M.D. Anderson Hospital (MDAH) stage III-B malignant melanoma with Newcastle disease virus oncolysate. [Abstract] Proceedings of the American Society of Clinical Oncology 9: A-1091, 281, 1990.
- Mallmann P, Eis-Hubinger AM, Krebs D: Lymphokine-activated tumor-infiltrating lymphocytes and autologous tumor vaccine in breast and ovarian cancer. Onkologie 15 (6): 490-6, 1992.
- Anton P, Kirchner H, Jonas U, et al.: Cytokines and tumor vaccination. Cancer Biother Radiopharm 11 (5): 315-8, 1996. [PUBMED Abstract]
- Csatary LK, Bakács T: Use of Newcastle disease virus vaccine (MTH-68/H) in a patient with high-grade glioblastoma. JAMA 281 (17): 1588-9, 1999. [PUBMED Abstract]
- Cassel WA, Murras DR, Torbin AH, et al.: Viral oncolysate in the management of malignant melanoma. I. Preparation of the oncolysate and measurement of immunologic responses. Cancer 40 (2): 672-9, 1977. [PUBMED Abstract]
- Murray DR, Cassel WA, Torbin AH, et al.: Viral oncolysate in the management of malignant melanoma. II. Clinical studies. Cancer 40 (2): 680-6, 1977. [PUBMED Abstract]
- Cassel WA, Murray DR: Treatment of stage II malignant melanoma patients with a Newcastle disease virus oncolysate. Nat Immun Cell Growth Regul 7 (5-6): 351-2, 1988. [PUBMED Abstract]
- Kirchner HH, Anton P, Atzpodien J: Adjuvant treatment of locally advanced renal cancer with autologous virus-modified tumor vaccines. World J Urol 13 (3): 171-3, 1995. [PUBMED Abstract]
- Proebstle TM, Staib G, Kaufmann R, et al.: Autologous active specific immunization (ASI) therapy for metastatic melanoma [abstract from Fifth World Conference on Cancers of the Skin]. [Abstract] Melanoma Res 3: A-133, 35, 1993.
- Schirrmacher V: [Anti-tumor vaccination] Zentralbl Chir 125 (Suppl 1): 33-6, 2000. [PUBMED Abstract]
- Pomer S, Thiele R, Staehler G, et al.: [Tumor vaccination in renal cell carcinoma with and without interleukin-2 (IL-2) as adjuvant. A clinical contribution to the development of effective active specific immunization] Urologe A 34 (3): 215-20, 1995. [PUBMED Abstract]
- Schirrmacher V, Schlag P, Liebrich W, et al.: Specific immunotherapy of colorectal carcinoma with Newcastle-disease virus-modified autologous tumor cells prepared from resected liver metastasis. Ann N Y Acad Sci 690: 364-6, 1993. [PUBMED Abstract]
- Fábián Z, Csatary CM, Szeberényi J, et al.: p53-independent endoplasmic reticulum stress-mediated cytotoxicity of a Newcastle disease virus strain in tumor cell lines. J Virol 81 (6): 2817-30, 2007. [PUBMED Abstract]
- Sinkovics J, Horvath J: New developments in the virus therapy of cancer: a historical review. Intervirology 36 (4): 193-214, 1993. [PUBMED Abstract]
- Fábián Z, Töröcsik B, Kiss K, et al.: Induction of apoptosis by a Newcastle disease virus vaccine (MTH-68/H) in PC12 rat phaeochromocytoma cells. Anticancer Res 21 (1A): 125-35, 2001 Jan-Feb. [PUBMED Abstract]
- Schirrmacher V, Bai L, Umansky V, et al.: Newcastle disease virus activates macrophages for anti-tumor activity. Int J Oncol 16 (2): 363-73, 2000. [PUBMED Abstract]
- Schirrmacher V, Heicappell R: Prevention of metastatic spread by postoperative immunotherapy with virally modified autologous tumor cells. II. Establishment of specific systemic anti-tumor immunity. Clin Exp Metastasis 5 (2): 147-56, 1987 Apr-Jun. [PUBMED Abstract]
- Wheelock EF, Dingle JH: Observations on the repeated administration of viruses to a patient with acute leukemia. A preliminary report. N Engl J Med 271(13): 645-51, 1964.
- Freeman AI, Zakay-Rones Z, Gomori JM, et al.: Phase I/II trial of intravenous NDV-HUJ oncolytic virus in recurrent glioblastoma multiforme. Mol Ther 13 (1): 221-8, 2006. [PUBMED Abstract]
- Liang W, Wang H, Sun TM, et al.: Application of autologous tumor cell vaccine and NDV vaccine in treatment of tumors of digestive tract. World J Gastroenterol 9 (3): 495-8, 2003. [PUBMED Abstract]