Effects of Newcastle Disease Virus on Human Cancer Cells
NDV and Cancer Immunotherapy

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.[1-12] Reviewed in [13,14] Several of these studies have provided much of the evidence that lytic strains of NDV are also oncolytic.[3-6,8-10,12] Reviewed in [13]

Strain 73-T, which is lytic, has been shown to kill the following types of human cancer cells in vitro : fibrosarcoma, osteosarcoma, neuroblastoma, bladder carcinoma, cervical carcinoma, melanoma, Wilms tumor, and myeloid leukemia;[3,6,8,9] however, this strain did not kill human B-cell lymphoma (i.e., Burkitt lymphoma) cells in vitro.[8] In addition, strain 73-T did not kill normal, proliferating human white blood cells or normal human skin fibroblasts in vitro,[3,6,8] but it killed normal human lung fibroblasts in vitro at the same rate that it killed cancer cells.[8]

Lytic strain Roakin has been reported to kill human B-cell lymphoma and human T-cell lymphoma (i.e., Hodgkin lymphoma) cells in vitro four to five times faster than it kills normal, resting human white blood cells.[4,5] This strain, however, has also been reported to kill normal, proliferating human white blood cells in vitro, though at a lower rate than it kills cancer cells.[4]

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.[12] The replication efficiency of this strain in normal human cells was not tested.

Overall, these results show that there are some types of human cancer cells in which individual lytic strains of NDV do not replicate very well and that there are some types of normal human cells in which they replicate very efficiently. Nonetheless, these data and the absence of serious illness in individuals infected with NDV Reviewed in [1-3,10,13,15-21] are consistent with the view that NDV replicates much more efficiently in human cancer cells than it does in most types of normal human cells.

NDV strain Ulster, which is nonlytic, has also been shown to replicate efficiently in human cancer cells in vitro, including cells of the following types of human tumors: colorectal carcinoma, gastric carcinoma, pancreatic carcinoma, bladder carcinoma, breast carcinoma, ovarian carcinoma, renal cell carcinoma, lung carcinoma, larynx carcinoma, cervical carcinoma, glioblastoma, melanoma, B-cell lymphoma, and T-cell lymphoma.[7] This strain does not replicate very efficiently in resting or proliferating normal human white blood cells in vitro.[7] Other experiments have shown that NDV Ulster can kill infected cells,[22] Reviewed in [14] and it can replicate in human cancer cells whether they are actively proliferating or not.[7] Reviewed in [20]

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.

Intratumoral injection of strain 73-T was associated with complete tumor regression in 75% to 100% of mice bearing human fibrosarcoma, neuroblastoma, or cervical carcinoma tumors.[1-3,10] Intratumoral injection of 73-T was also associated with more than 80% tumor regression in 66% of mice bearing human synovial sarcoma tumors.[2] In addition, intratumoral injection of 73-T was associated with 68% to 96% inhibition of tumor growth in mice bearing human epidermoid, colon, lung, breast, or prostate carcinoma tumors.[10]

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, however, was not affected, suggesting that the virus was unable to disseminate widely throughout the body.[11] Reviewed in [14,20]

Replication of strain 73-T in the above-mentioned neuroblastoma xenografts was demonstrated by showing an increase in the amount of virus that could be recovered from tumor samples over time.[1] When this strain was injected into the thigh muscle of athymic, nude mice, the amount of virus that could be recovered decreased with time,[1] a finding consistent with the proposal that NDV replicates much more efficiently in cancer cells than in most normal cells.

In one study, mice bearing human neuroblastoma xenografts were given single intraperitoneal injections of strain 73-T, and 9 (75%) of 12 treated mice exhibited complete, durable tumor regressions.[10]

It is important to note that athymic, nude mice still make small numbers of T cells, and they produce interferons, natural killer cells, and macrophages. Reviewed in [11,23,24] The possibility that these residual components of the immune system, which may be activated by the presence of NDV, contributed to the antitumor effects observed in the xenograft studies cannot be ruled out.

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.[6,8,22,25-37] Reviewed in [11,20,38-42] A few of these studies used human cells,[6,8,26,27,35] Reviewed in [20,39,42] but most used animal cells and animal tumor models.[6,8,22,25,27-34,36] Reviewed in [11,20,38-41]

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: no major side effects were observed in any of the patients.[43]

Two in vitro studies have shown that infection of human immune system cells with NDV causes the cells to produce and release the cytokines interferon-alpha and tumor necrosis factor (TNF)-alpha.[6,8] In one of these studies,[6] it was shown further that infection of human cancer cells with NDV makes the cells more sensitive to the cytotoxic effects of TNF-alpha.

Additional 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.[8,26,27] The NDV protein hemagglutinin-neuraminidase, which is present in the plasma membrane of virus-infected cells, appears to play a role in the enhancement of T cell activation. There is evidence that this protein makes infected cells more adhesive, thereby promoting the interaction between virus-infected cells and immune system cells.[27] Reviewed in [20]

Other 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.[26,35] Reviewed in [20,39,42] It has been reported that this improved interaction leads to better T cell activation.[26,35] Reviewed in [20,39,42] T cells exposed to NDV-infected human colon cancer cells and bispecific monoclonal antibodies showed not only an increased ability to kill the virus-infected cells but also an ability to inhibit the proliferation of uninfected colon cancer cells.[26,35] Reviewed in [20] On the basis of these and other in vitro findings, it has been proposed that vaccines consisting of NDV-infected cancer cells and bispecific monoclonal antibodies be tested in humans.[20,26,35,39,42]

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;[22,25,28,32-34,36,37] Reviewed in [11,20,38-42] however, additional experiments have utilized one or more of the following tumor models: mouse B16 melanoma,[30] mouse Lewis lung carcinoma,[29,32] mouse P815 mastocytoma,[32] mouse Ca 761-P93 mammary carcinoma,[32] and guinea pig L10 hepatocellular carcinoma.[31]

In one study,[32] it was shown that anticancer activity could be induced in mouse macrophages both in vitro and in vivo by infection with NDV strain Ulster. Similar activation of mouse macrophages in vitro was observed after infection with the NDV lytic strain Lasota. In this study, the activated macrophages showed cytotoxic activity toward ESb, P815 mastocytoma, and Ca 761-P93 mammary carcinoma cells in vitro. Other experiments demonstrated that much of the observed anticancer activity could be attributed to the production and release of TNF-alpha by the infected macrophages. In addition, the infected, activated macrophages showed anticancer activity in vivo when they were injected into mice bearing Ca 761-P93 mammary carcinoma or Lewis lung carcinoma tumors.[32]

In another study, Reviewed in [11] intratumoral injection of NDV strain Ulster into growing ESb tumors in immunocompetent mice led to a cessation of tumor growth and an absence of metastases in 42% of treated animals. In the remaining mice, tumor growth and metastatic spread continued at the same rate as in control animals. Reviewed in [11] Additional results from this study indicated that the anticancer effect in the responding animals was due primarily to the activation of T cells directed against a tumor-specific antigen on ESb cells rather than a virus antigen. Reviewed in [11]

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.[22,25,28,33,34,36] Reviewed in [11,20,38,40,41] At least four studies [22,25,34,36] Reviewed in [40,41] have shown that T cells isolated from mice that have growing ESb tumors can be activated in vitro by co-culture with NDV-infected ESb cells and that the resulting activated T cells possess an enhanced ability to kill uninfected ESb cells in vitro. In addition, two in vivo studies [28] Reviewed in [11] have shown that mice injected with NDV-infected, irradiated ESb cells are 30 to 250 times more resistant to later injection with proliferating ESb cells than mice that are initially injected with uninfected, irradiated ESb cells. Furthermore, at least two in vivo studies have demonstrated that vaccination of mice with NDV-infected, irradiated ESb cells after surgery to remove a growing ESb primary tumor can prevent the growth of metastatic tumors in approximately 50% of treated animals.[28,33] Reviewed in [11,38,40,41] When the surviving mice were subsequently injected with proliferating ESb cells, they all remained free of cancer, indicating that the NDV/tumor cell vaccine had conferred anticancer immunity.[28,33] Reviewed in [11,40,41] Similar results were obtained from in vivo studies that employed the mouse B16 melanoma model,[30] the mouse Lewis lung carcinoma model,[29] or the guinea pig L10 hepatocellular carcinoma model.[31]

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.[30]

References

1. 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]
   
   
2. 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]
   
   
3. 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]
   
   
4. 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]
   
   
5. 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]
   
   
6. 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]
   
   
7. 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]
   
   
8. 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]
   
   
9. Cassel WA, Garrett RE: Newcastle disease virus as an antineoplastic agent. Cancer 18: 863-8, 1965. 
   
   
10. 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]
    
    
11. Schirrmacher V, Ahlert T, Heicappell R, et al.: Successful application of non-oncogenic viruses for antimetastatic cancer immunotherapy. Cancer Rev 5: 19-49, 1986. 
    
    
12. 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]
    
    
13. Kirn DH, McCormick F: Replicating viruses as selective cancer therapeutics. Mol Med Today 2 (12): 519-27, 1996.  [PUBMED Abstract]
    
    
14. 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]
    
    
15. 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]
    
    
16. Emergency Preparedness Information eXchange.: Foreign Animal Diseases: Newcastle Disease. Burnaby, B.C., Canada: Telematics Research Lab, Simon Fraser University, 2002. Available online. ¹ Last accessed May 2, 2006. 
    
    
17. 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]
    
    
18. 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]
    
    
19. 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]
    
    
20. Schirrmacher V, Ahlert T, Pröbstle T, et al.: Immunization with virus-modified tumor cells. Semin Oncol 25 (6): 677-96, 1998.  [PUBMED Abstract]
    
    
21. Moss RW: Alternative pharmacological and biological treatments for cancer: ten promising approaches. J Naturopathic Med 6 (1): 23-32, 1996. 
    
    
22. 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]
    
    
23. Kadish AS, Doyle AT, Steinhauer EH, et al.: Natural cytotoxicity and interferon production in human cancer: deficient natural killer activity and normal interferon production in patients with advanced disease. J Immunol 127 (5): 1817-22, 1981.  [PUBMED Abstract]
    
    
24. Budzynski W, Radzikowski C: Cytotoxic cells in immunodeficient athymic mice. Immunopharmacol Immunotoxicol 16 (3): 319-46, 1994.  [PUBMED Abstract]
    
    
25. 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]
    
    
26. 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]
    
    
27. 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]
    
    
28. 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]
    
    
29. 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]
    
    
30. 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]
    
    
31. 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]
    
    
32. 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]
    
    
33. 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]
    
    
34. von Hoegen P, Zawatzky R, Schirrmacher V: Modification of tumor cells by a low dose of Newcastle disease virus. III. Potentiation of tumor-specific cytolytic T cell activity via induction of interferon-alpha/beta. Cell Immunol 126 (1): 80-90, 1990.  [PUBMED Abstract]
    
    
35. Haas C, Strauss G, Moldenhauer G, et al.: Bispecific antibodies increase T-cell stimulatory capacity in vitro of human autologous virus-modified tumor vaccine. Clin Cancer Res 4 (3): 721-30, 1998.  [PUBMED Abstract]
    
    
36. Von Hoegen P, Weber E, Schirrmacher V: Modification of tumor cells by a low dose of Newcastle disease virus. Augmentation of the tumor-specific T cell response in the absence of an anti-viral response. Eur J Immunol 18 (8): 1159-66, 1988.  [PUBMED Abstract]
    
    
37. Schirrmacher V, Schild HJ, Gückel B, et al.: Tumour-specific CTL response requiring interactions of four different cell types and recognition of MHC class I and class II restricted tumour antigens. Immunol Cell Biol 71 ( Pt 4): 311-26, 1993.  [PUBMED Abstract]
    
    
38. Schirrmacher V: Active specific immunotherapy: a new modality of cancer treatment involving the patient's own immune system. Onkologie 16: 290-6, 1993. 
    
    
39. Haas C, Schirrmacher V: Immunogenicity increase of autologous tumor cell vaccines by virus infection and attachment of bispecific antibodies. Cancer Immunol Immunother 43 (3): 190-4, 1996.  [PUBMED Abstract]
    
    
40. Schirrmacher V, von Hoegen P, Heicappell R: Virus modified tumor cell vaccines for active specific immunotherapy of micrometastases: expansion and activation of tumor-specific T cells. Prog Clin Biol Res 288: 391-9, 1989.  [PUBMED Abstract]
    
    
41. Schirrmacher V, von Hoegen P, Heicappell R: Postoperative activation of tumor specific T cells by immunization with virus-modified tumor cells and effects on metastasis. Adv Exp Med Biol 233: 91-6, 1988.  [PUBMED Abstract]
    
    
42. Schirrmacher V, Haas C: Modification of cancer vaccines by virus infection and attachment of bispecific antibodies. In: Walden P, Trefzer U, Sterry W, et al., eds.: Gene Therapy of Cancer. New York, NY: Plenum Press, 1998, pp 251-7. 
    
    
43. Karcher J, Dyckhoff G, Beckhove P, et al.: Antitumor vaccination in patients with head and neck squamous cell carcinomas with autologous virus-modified tumor cells. Cancer Res 64 (21): 8057-61, 2004.  [PUBMED Abstract]
    
    

Glossary Terms

A type of laboratory mouse that is hairless, lacks a normal thymus gland, and has a defective immune system because of a genetic mutation. Athymic nude mice are often used in cancer research because they do not reject tumor cells, from mice or other species.

A white blood cell that comes from bone marrow. As part of the immune system, B cells make antibodies and help fight infections. Also called B lymphocyte.

A monoclonal antibody that binds two different types of antigen. Bispecific monoclonal antibodies do not occur naturally; they must be made in the laboratory.

The organ that stores urine.

Glandular organ located on the chest. The breast is made up of connective tissue, fat, and breast tissue that contains the glands that can make milk. Also called mammary gland.

An aggressive (fast-growing) type of B-cell non-Hodgkin lymphoma that occurs most often in children and young adults. The disease may affect the jaw, central nervous system, bowel, kidneys, ovaries, or other organs. There are three main types of Burkitt lymphoma (sporadic, endemic, and immunodeficiency related). Sporadic Burkitt lymphoma occurs throughout the world, and endemic Burkitt lymphoma occurs in Africa. Immunodeficiency-related Burkitt lymphoma is most often seen in AIDS patients.

Cancer that begins in the skin or in tissues that line or cover internal organs.

The individual unit that makes up the tissues of the body. All living things are made up of one or more cells.

Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck. Cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the “neck”) of the uterus.

A mixture of two or more different kinds of cells that are grown together.

Having to do with the colon or the rectum.

An animal in a study that does not receive the treatment being tested. Comparing the health of control animals with the health of treated animals allows researchers to evaluate the effects of a treatment more accurately.

A substance that is produced by cells of the immune system and can affect the immune response. Cytokines can also be produced in the laboratory by recombinant DNA technology and given to people to affect immune responses.

Cell-killing.

A type of white blood cell that can directly destroy specific cells. T cells can be separated from other blood cells, grown in the laboratory, and then given to a patient to destroy tumor cells. Certain cytokines can also be given to a patient to help form cytotoxic T cells in the patient's body.

Cancer that begins in squamous cells (thin, flat cells that look like fish scales). Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the lining of the respiratory and digestive tracts. Also called squamous cell carcinoma.

A connective tissue cell that makes and secretes collagen proteins.

A type of soft tissue sarcoma that begins in fibrous tissue, which holds bones, muscles, and other organs in place.

Having to do with the stomach.

A fast-growing type of central nervous system tumor that forms from glial (supportive) tissue of the brain and spinal cord and has cells that look very different from normal cells. Glioblastoma usually occurs in adults and affects the brain more often than the spinal cord. Also called grade IV astrocytoma, glioblastoma multiforme, and GBM.

A type of white blood cell that helps stimulate immune system reactions. Helper T cells help activate cytotoxic T cells and macrophages by secreting cytokines. They also stimulate B cells to make antibodies.

A protein found in the outer coat of paramyxoviruses. This protein helps virus particles bind to cells, making infection easier.

A type of adenocarcinoma, the most common type of liver tumor.

A cancer of the immune system that is marked by the presence of a type of cell called the Reed-Sternberg cell. The two major types of Hodgkin disease are classical Hodgkin lymphoma and nodular lymphocyte-predominant Hodgkin lymphoma. Symptoms include the painless enlargement of lymph nodes, spleen, or other immune tissue. Other symptoms include fever, weight loss, fatigue, or night sweats. Also called Hodgkin lymphoma.

The complex group of organs and cells that defends the body against infections and other diseases.

Having the ability to produce a normal immune response.

Treatment to boost or restore the ability of the immune system to fight cancer, infections, and other diseases. Also used to lessen certain side effects that may be caused by some cancer treatments. Agents used in immunotherapy include monoclonal antibodies, growth factors, and vaccines. These agents may also have a direct antitumor effect. Also called biological therapy, biotherapy, biological response modifier therapy, and BRM therapy.

In the laboratory (outside the body). The opposite of in vivo (in the body).

In the body. The opposite of in vitro (outside the body or in the laboratory).

Invasion and multiplication of germs in the body. Infections can occur in any part of the body and can spread throughout the body. The germs may be bacteria, viruses, yeast, or fungi. They can cause a fever and other problems, depending on where the infection occurs. When the body’s natural defense system is strong, it can often fight the germs and prevent infection. Some cancer treatments can weaken the natural defense system.

Use of a syringe and needle to push fluids or drugs into the body; often called a "shot."

A biological response modifier (a substance that can improve the body's natural response to infections and other diseases). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and -gamma. The body normally produces these substances. They are also made in the laboratory to treat cancer and other diseases.

Within the skin. Also called intracutaneous.

Within a tumor.

Treated with radiation.

Research done in a laboratory. These studies may use test tubes or animals to find out if a drug, procedure, or treatment is likely to be useful. Laboratory studies take place before any testing is done in humans.

The area of the throat containing the vocal cords and used for breathing, swallowing, and talking. Also called voice box.

Cancer that starts in blood-forming tissue such as the bone marrow and causes large numbers of blood cells to be produced and enter the bloodstream.

One of a pair of organs in the chest that supplies the body with oxygen, and removes carbon dioxide from the body.

Cancer that begins in cells of the immune system. There are two basic categories of lymphomas. One kind is Hodgkin lymphoma, which is marked by the presence of a type of cell called the Reed-Sternberg cell. The other category is non-Hodgkin lymphomas, which includes a large, diverse group of cancers of immune system cells. Non-Hodgkin lymphomas can be further divided into cancers that have an indolent (slow-growing) course and those that have an aggressive (fast-growing) course. These subtypes behave and respond to treatment differently. Both Hodgkin and non-Hodgkin lymphomas can occur in children and adults, and prognosis and treatment depend on the stage and the type of cancer.

Having to do with lysis. In biology, lysis refers to the disintegration of a cell by disruption of its plasma membrane. Lysis can be caused by chemical or physical means (e.g., high-energy sound waves) or by a virus infection.

A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells.

Having to do with the breast.

A growth or lump of mast cells (a type of white blood cell). Mast cell tumors can involve the skin, subcutaneous tissue, and muscle tissue. Also called mast cell tumor.

A form of cancer that begins in melanocytes (cells that make the pigment melanin). It may begin in a mole (skin melanoma), but can also begin in other pigmented tissues, such as in the eye or in the intestines.

The spread of cancer from one part of the body to another. A tumor formed by cells that have spread is called a “metastatic tumor” or a “metastasis.” The metastatic tumor contains cells that are like those in the original (primary) tumor. The plural form of metastasis is metastases (meh-TAS-tuh-SEEZ).

Having to do with metastasis, which is the spread of cancer from one part of the body to another.

A type of protein made in the laboratory that can locate and bind to substances in the body, including tumor cells. There are many kinds of monoclonal antibodies. Each monoclonal antibody is made to find one substance. Monoclonal antibodies are being used to treat some types of cancer and are being studied in the treatment of other types. They can be used alone or to carry drugs, toxins, or radioactive materials directly to a tumor.

Having to do with or resembling the bone marrow. May also refer to certain types of hematopoietic (blood-forming) cells found in the bone marrow. Sometimes used as a synonym for myelogenous; for example, acute myeloid leukemia and acute myelogenous leukemia are the same disease.

NK cell. A type of white blood cell that contains granules with enzymes that can kill tumor cells or microbial cells. Also called large granular lymphocyte and NK cell.

Cancer that arises in immature nerve cells and affects mostly infants and children.

In biology, refers to viruses that do not kill infected cells by disrupting their plasma membranes.

A cancer of the bone that usually affects the large bones of the arm or leg. It occurs most commonly in young people and affects more males than females. Also called osteogenic sarcoma.

Having to do with the ovaries, the female reproductive glands in which the ova (eggs) are formed. The ovaries are located in the pelvis, one on each side of the uterus.

Having to do with the pancreas.

The outer membrane of a cell.

Research using animals to find out if a drug, procedure, or treatment is likely to be useful. Preclinical studies take place before any testing in humans is done.

The original tumor.

Multiplying or increasing in number. In biology, cell proliferation occurs by a process known as cell division.

A molecule made up of amino acids that are needed for the body to function properly. Proteins are the basis of body structures such as skin and hair and of substances such as enzymes, cytokines, and antibodies.

A decrease in the size of a tumor or in the extent of cancer in the body.

The most common type of kidney cancer. It begins in the lining of the renal tubules in the kidney. The renal tubules filter the blood and produce urine. Also called hypernephroma.

To make a copy or duplicate of something.

In biology, refers to a cell that is not dividing.

Flat cell that looks like a fish scale under a microscope. These cells cover inside and outside surfaces of the body. They are found in the tissues that form the surface of the skin, the lining of the hollow organs of the body (such as the bladder, kidney, and uterus), and the passages of the respiratory and digestive tracts.

Beneath the skin.

A malignant tumor that develops in the synovial membrane of the joints.

One type of white blood cell that attacks virus-infected cells, foreign cells, and cancer cells. T cells also produce a number of substances that regulate the immune response. Also called T lymphocyte.

A disease in which certain cells of the lymph system (called T lymphocytes) become cancerous.

An abnormal mass of tissue that results when cells divide more than they should or do not die when they should. Tumors may be benign (not cancerous), or malignant (cancerous). Also called neoplasm.

Refers to the number of cancer cells, the size of a tumor, or the amount of cancer in the body. Also called tumor load.

Cells, tissues, or animals used to study the development and progression of cancer, and to test new treatments before they are given to humans. Animals with transplanted human tumors or other tissues are called xenograft models.

A protein made by white blood cells in response to an antigen (substance that causes the immune system to make a specific immune response) or infection. Tumor necrosis factor can also be made in the laboratory. It may boost a person’s immune response, and also may cause necrosis (cell death) of some types of tumor cells. Tumor necrosis factor is being studied in the treatment of some types of cancer. It is a type of cytokine. Also called TNF.

A protein or other molecule that is unique to cancer cells or is much more abundant in them. These molecules are usually found in the plasma (outer) membrane, and they are thought to be potential targets for immunotherapy or other types of anticancer treatment.

Treatment with a vaccine.

A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. A vaccine can help the body recognize and destroy cancer cells or microorganisms.

In medicine, a very simple microorganism that infects cells and may cause disease. Because viruses can multiply only inside infected cells, they are not considered to be alive.

Refers to a blood cell that does not contain hemoglobin. White blood cells include lymphocytes, neutrophils, eosinophils, macrophages, and mast cells. These cells are made by bone marrow and help the body fight infections and other diseases. Also called WBC.

A disease in which malignant (cancer) cells are found in the kidney, and may spread to the lungs, liver, or nearby lymph nodes. Wilms tumor usually occurs in children younger than 5 years old.

The cells of one species transplanted to another species.