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Encyclopedia > Oncolytic virus


An oncolytic virus is a virus used to treat cancer due to their ability to specifically infect cancer cells, while leaving normal cells unharmed. Viruses can be engineered to be replication competent only in cancer cells, leading to cell lysis and dose amplification at the site of the tumour. Replication competent viruses can efficiently deliver anticancer genes to cancer cells and also have an inherent ability to lyse tumour cells. Orders A virus is a submicroscopic particle that can infect the cells of a biological organism. ... When normal cells are damaged beyond repair, they are eliminated by apoptosis. ... When normal cells are damaged or old they undergo apoptosis; cancer cells, however, avoid apoptosis. ... A common alternate meaning of virus is computer virus. ... When normal cells are damaged or old they undergo apoptosis; cancer cells, however, avoid apoptosis. ... Lysis (Greek lusis from luein = to separate) refers to the death of a cell by bursting, often by viral or osmotic mechanisms that compromise the integrity of the cellular membrane. ... When normal cells are damaged or old they undergo apoptosis; cancer cells, however, avoid apoptosis. ...

Contents


Requirements for an Oncolytic Virus

The virus should be able to tolerate storage, and production at high titres. A double stranded DNA genome is advantageous because it has greater stability during storage, and reduces the chances of hazardous mutations. Viruses like adenoviruses and herpes simplex virus are the most suitable, and have been the most extensively studied. In biology the genome of an organism is the whole hereditary information of an organism that is encoded in the DNA (or, for some viruses, RNA). ... This article is about mutation in biology, for other meanings see: mutation (disambiguation). ... Genera Mastadenovirus Aviadenovirus Atadenovirus Siadenovirus Adenoviruses are viruses of the family Adenoviridae. ... The herpes simplex virus (HSV) (also known as Cold Sore, Night Fever, or Fever Blister) is a virus that manifests itself in two common viral infections, each marked by painful, watery blisters in the skin or mucous membranes (such as the mouth or lips) or on the genitals. ...


Generating Tumour Selectivity

There are two main approaches for generating tumour selectivity: transductional and non-transductional targeting. Transductional targeting involves modifying the specificity of viral coat protein, thus increasing entry into target cells while reducing entry to non-target cells. Non-transductional targeting involves altering the genome of the virus so it can only replicate in cancer cells. This can be done by either transcription targeting, where genes essential for viral replication are placed under the control of a tumour-specific promoter, or by attenuation, which involves introducing deletions into the viral genome that eliminate functions that are dispensable in cancer cells, but not in normal cells. There are also other, slightly more obscure methods. In biology the genome of an organism is the whole hereditary information of an organism that is encoded in the DNA (or, for some viruses, RNA). ... When normal cells are damaged or old they undergo apoptosis; cancer cells, however, avoid apoptosis. ... Transcription may be one of the following: In linguistics, transcription is the conversion of spoken words into written language. ... This stylistic schematic diagram shows a gene in relation to the double helix structure of DNA and to a chromosome (right). ... Replication may mean: In biology: Self-replication, when a molecule (or any other pattern) makes a copy of itself DNA replication, the act of copying the genetic material of a cell (DNA) to a daughter cell Semiconservative replication, mechanism of DNA replication Other: replication (computer science), the provision of redundant... In genetics, a promoter is a DNA sequence that enables a gene to be transcribed. ... Attenuation is the decrease of the amount, force, magnitude, or value of something. ... In biology the genome of an organism is the whole hereditary information of an organism that is encoded in the DNA (or, for some viruses, RNA). ... When normal cells are damaged or old they undergo apoptosis; cancer cells, however, avoid apoptosis. ...


Transductional Targeting

This approach to tumour selectivity has mainly focused on adenoviruses, although it is entirely viable with other viruses. However, it should be recognised that increasing the host tissue range of a virus has serious safety implications. Genera Mastadenovirus Aviadenovirus Atadenovirus Siadenovirus Adenoviruses are viruses of the family Adenoviridae. ...


The most commonly used group of adenoviruses is serotype 5 (Ad5), whose binding to host cells is initiated by interactions between the cellular coxsackievirus and adenovirus receptor (CAR), and the knob domain of the adenovirus coat protein trimer. Li et al (1999) showed that CAR is necessary for adenovirus infection by showing that CAR-negative cells could be made adenovirus-sensitive by transfection with CAR cDNA. Virus internalisation depends on an Arginine-Glycine-Asparagine (RGD) motif at the base of adenovirus coat protein that binds to integrins, causing endocytosis. It has been suggested that CAR has a role in cell adhesion, and possibly tumour suppression. Although expressed widely in epithelial cells, CAR expression in tumours is extremely variable, leading to resistance to Ad5 infection. Retargeting of Ad5 from CAR, to another receptor that is ubiquitously expressed on cancer cells, enables reduction of Ad5 tropism, enhancing infection of CAR deficient target cells. This can be done in one of two ways: Genera Mastadenovirus Aviadenovirus Atadenovirus Siadenovirus Adenoviruses are viruses of the family Adenoviridae. ... Genera Mastadenovirus Aviadenovirus Atadenovirus Siadenovirus Adenoviruses are viruses of the family Adenoviridae. ... In biochemistry, a receptor is a protein on the cell membrane or within the cytoplasm or cell nucleus that binds to a specific molecule (a ligand), such as a neurotransmitter, hormone, or other substance, and initiates the cellular response to the ligand. ... Genera Mastadenovirus Aviadenovirus Atadenovirus Siadenovirus Adenoviruses are viruses of the family Adenoviridae. ... In biochemistry, a trimer is a macromolecular compound formed by three non-covalently bound macromolecules. ... Genera Mastadenovirus Aviadenovirus Atadenovirus Siadenovirus Adenoviruses are viruses of the family Adenoviridae. ... Genera Mastadenovirus Aviadenovirus Atadenovirus Siadenovirus Adenoviruses are viruses of the family Adenoviridae. ... Introducing DNA into eukaryotic cells, such as animal cells, is called transfection. ... In genetics, complementary DNA (cDNA) is single-stranded DNA synthesized from a mature mRNA template. ... Arginine (Arg) is an α-amino acid. ... Glycine (Gly, G) is a nonpolar amino acid. ... Asparagine is one of the 20 most common natural amino acids on Earth. ... Genera Mastadenovirus Aviadenovirus Atadenovirus Siadenovirus Adenoviruses are viruses of the family Adenoviridae. ... An integrin, or integrin receptor, is an integral membrane protein in the plasma membrane of cells. ... Endocytosis is a process whereby cells absorb material (molecules such as proteins) from outside by engulfing it with their cell membrane. ... In zootomy, epithelium is a tissue composed of a layer of cells. ... In biochemistry, a receptor is a protein on the cell membrane or within the cytoplasm or cell nucleus that binds to a specific molecule (a ligand), such as a neurotransmitter, hormone, or other substance, and initiates the cellular response to the ligand. ... When normal cells are damaged or old they undergo apoptosis; cancer cells, however, avoid apoptosis. ... Phycomyces, a fungus, also exhibit phototropism A tropism is a biological phenomenon, indicating growth or turning movement of a biological organism, usually a plant, in response to an environmental stimulus. ...


Adapter Molecules

Bi-specific adapter molecules can be administered along with the virus to redirect viral coat protein tropism. These molecules are fusion proteins that are made up of an antibody raised against the knob domain of the adenovirus coat protein, fused to a natural ligand for a cell surface receptor. The use of adapter molecules has been shown to increase viral transduction. However, adapters add complexity to the system, and the effect of adapter molecule binding on the stability of the virus is uncertain. A fusion protein is a protein created through genetic engineering from two or more proteins/peptides. ... Schematic of antibody binding to an antigen An antibody is a protein used by the immune system to identify and neutralize foreign objects like bacteria and viruses. ... Genera Mastadenovirus Aviadenovirus Atadenovirus Siadenovirus Adenoviruses are viruses of the family Adenoviridae. ... In chemistry, a ligand is an atom, ion, or molecule (see also: functional group), that donates one or more of its electrons through a coordinate covalent bond to, or shares its electrons through a covalent bond with one or more central atoms or ions, usually metals. ... In biochemistry, a receptor is a protein on the cell membrane or within the cytoplasm or cell nucleus that binds to a specific molecule (a ligand), such as a neurotransmitter, hormone, or other substance, and initiates the cellular response to the ligand. ...


Coat Protein Modification

This method involves genetically modifying the fiber knob domain of the viral coat protein to alter its specificity. Wickham et al (2003) added short peptides to the C-terminal end of the coat protein, which successfully altered viral tropism. The addition of larger peptides to the C-terminus is not viable because it reduces adenovirus integrity, possibly due to an effect on fiber trimerisation. The fiber protein also contains a HI-loop structure, which can tolerate peptide insertions of up to 100 residues without any negative effects on adenovirus integrity. Davydova et al (2004) inserted an RGD motif in the HI loop of the fiber knob protein, shifting specificity toward integrins, which are frequently over-expressed in Oesophageal Adenocarcinoma. When combined with a form of non-transductional targeting, these viruses proved to be effective and selective therapeutic agents for Oesophageal Adenocarcinoma. Peptides (from the Greek πεπτος, digestible), are the family of short molecules formed from the linking, in a defined order, of various α-amino acids. ... The C-terminal end refers to the extremity of a protein or polypeptide terminated by an amino acid with a free carboxyl group (COOH). ... Peptides (from the Greek πεπτος, digestible), are the family of short molecules formed from the linking, in a defined order, of various α-amino acids. ... Genera Mastadenovirus Aviadenovirus Atadenovirus Siadenovirus Adenoviruses are viruses of the family Adenoviridae. ... Peptides (from the Greek πεπτος, digestible), are the family of short molecules formed from the linking, in a defined order, of various α-amino acids. ... Genera Mastadenovirus Aviadenovirus Atadenovirus Siadenovirus Adenoviruses are viruses of the family Adenoviridae. ... An integrin, or integrin receptor, is an integral membrane protein in the plasma membrane of cells. ...


Non-Transductional Targeting

Transcriptional Targeting

Transcriptional targeting places an essential viral gene under the control of a tumour-specific promoter, meaning the gene is only expressed in cell types where all the transcription factors required for promoter function are active. A suitable promoter should be active in the tumour but inactive in the majority of normal tissue, particularly the liver, which is the organ that is most exposed to blood born viruses. Many such promoters have been identified and studied for the treatment of a range of cancers. This stylistic schematic diagram shows a gene in relation to the double helix structure of DNA and to a chromosome (right). ... In genetics, a promoter is a DNA sequence that enables a gene to be transcribed. ... This stylistic schematic diagram shows a gene in relation to the double helix structure of DNA and to a chromosome (right). ... In molecular biology, a transcription factor is a protein that binds DNA at a specific promoter or enhancer region or site, where it regulates transcription. ... In genetics, a promoter is a DNA sequence that enables a gene to be transcribed. ... In genetics, a promoter is a DNA sequence that enables a gene to be transcribed. ... The liver is the largest internal organ of the human body. ... In genetics, a promoter is a DNA sequence that enables a gene to be transcribed. ...


Cyclooxygenase-2 enzyme (Cox-2) expression is elevated in a range of cancers, and has low liver expression, making it a suitable tumour-specific promoter. Davydova et al (2004) targeted AdCox2Lluc, a conditionally replicating adenovirus (CRAd), against Oesophageal Adenocarcinoma by placing the early genes under the control of a Cox-2 promoter (adenoviruses have two early genes, E1A and E1B, that are essential for replication). When combined with transductional targeting, AdCox2Lluc showed potential for treatment of Oesophageal Adenocarcinoma. Cox-2 is also a possible tumour-specific promoter candidate for other cancer types, including ovarian cancer. Ribbon diagram of the enzyme TIM. TIM is catalytically perfect, meaning its conversion rate is limited, or nearly limited to its substrate diffusion rate. ... In genetics, a promoter is a DNA sequence that enables a gene to be transcribed. ... Genera Mastadenovirus Aviadenovirus Atadenovirus Siadenovirus Adenoviruses are viruses of the family Adenoviridae. ... In genetics, a promoter is a DNA sequence that enables a gene to be transcribed. ... Genera Mastadenovirus Aviadenovirus Atadenovirus Siadenovirus Adenoviruses are viruses of the family Adenoviridae. ... In genetics, a promoter is a DNA sequence that enables a gene to be transcribed. ...


A suitable tumour-specific promoter for Prostate Cancer is prostate specific antigen (PSA), whose expression is greatly elevated in prostate cancer. CN706 is a CRAd with a PSA tumour-specific promoter driving expression of the adenoviral E1A gene, required for viral replication. Rodriguez et al (1997) showed that the CN706 titre is significantly greater in PSA-positive cells. In genetics, a promoter is a DNA sequence that enables a gene to be transcribed. ... Prostate cancer is a disease in which cancer develops in the prostate, a gland in the male reproductive system. ... An antigen is a substance that stimulates an immune response, especially the production of antibodies. ... Prostate cancer is a disease in which cancer develops in the prostate, a gland in the male reproductive system. ... In genetics, a promoter is a DNA sequence that enables a gene to be transcribed. ... This stylistic schematic diagram shows a gene in relation to the double helix structure of DNA and to a chromosome (right). ...


Attenuation

Cancer cells and virus-infected cells have similar alterations in their cell signalling pathways, particularly those that govern progression through the cell cycle. A viral gene whose function is to alter a pathway is dispensable in cells where the pathway is defective, but not in cells where the pathway is active. Attenuation involves deleting viral genes, or gene regions, to eliminate viral functions that are expendable in tumour cell, but not in normal cells. When normal cells are damaged or old they undergo apoptosis; cancer cells, however, avoid apoptosis. ... The cell cycle, or cell-division cycle (CDC), is the cycle of events in a eukaryotic cell from one cell division to the next. ... This stylistic schematic diagram shows a gene in relation to the double helix structure of DNA and to a chromosome (right). ...


For adenovirus replication to occur, the host cell must be induced into S-phase by viral proteins interfering with cell cycle proteins. The adenoviral E1A gene is responsible for inactivation of several proteins, including Retinoblastoma, allowing entry into S-phase. The adenovirus E1B gene inactivates p53, preventing apoptosis. Adenoviruses with mutant E1B have been shown to replicate selectively in p53 deficient cells. One of these viruses, ONYX-015, has a deletion in the E1B coding region, preventing E1B expression, has been shown to be capable of tumour-selective ‘tissue destruction’ in head and neck cancer. ONYX-015 combined with chemotherapy proved effective in a high proportion of cases, and has progressed to phase III clinical trials. However, research into ONYX-015 has been discontinued indefinitely for financial reasons. Genera Mastadenovirus Aviadenovirus Atadenovirus Siadenovirus Adenoviruses are viruses of the family Adenoviridae. ... The cell cycle, or cell-division cycle (CDC), is the cycle of events in a eukaryotic cell from one cell division to the next. ... This stylistic schematic diagram shows a gene in relation to the double helix structure of DNA and to a chromosome (right). ... Retinoblastoma is a cancer of the retina. ... Genera Mastadenovirus Aviadenovirus Atadenovirus Siadenovirus Adenoviruses are viruses of the family Adenoviridae. ... TP53 bound to a short DNA fragment. ... A cell undergoing apoptosis. ... Genera Mastadenovirus Aviadenovirus Atadenovirus Siadenovirus Adenoviruses are viruses of the family Adenoviridae. ... A mutant (also known to early geneticists as a monster) is an individual, organism, or new genetic character arising or resulting from an instance of mutation, which is a sudden structural change within the DNA of a gene or chromosome of an organism resulting in the creation of a new... TP53 bound to a short DNA fragment. ... The coding region of a gene is the portion of DNA that is transcribed into mRNA and translated into proteins. ... Chemotherapy is the use of chemical substances to treat disease. ... In medicine, a clinical trial (synonyms: clinical studies, research protocols, medical research) is a research study. ...


Carette et al (2004) used Ad5- Δ24E3, a CRAd with a 24 base pair deletion in the retinoblastoma-binding domain of the E1A protein, making it unable to silence retinoblastoma, and therefore unable to induce S-phase in host cells. This means Ad5-Δ24E3 is only able to replicate in proliferating cells, such as tumour cells. The adenovirus was used to deliver short hairpin RNA, which was able to reduce expression of the luciferase target gene in target cells to 30%, relative to the control, by RNA interference. Headline text this website sucks your mothers dickIn molecular biology, two nucleotides on opposite complementary DNA or RNA strands that are connected via hydrogen bonds are called a base pair (often abbreviated bp). ... Retinoblastoma is a cancer of the retina. ... A representation of the 3D structure of myoglobin, showing coloured alpha helices. ... Retinoblastoma is a cancer of the retina. ... Genera Mastadenovirus Aviadenovirus Atadenovirus Siadenovirus Adenoviruses are viruses of the family Adenoviridae. ... Luciferase is a generic name for enzymes commonly used in nature for bioluminescence. ... It has been suggested that Antisense RNA be merged into this article or section. ...


The herpes simplex virus genome contains the enzymes thymidine kinase and ribonucleotide reductase, whose cellular forms are responsible for the production of dNTP’s required for DNA synthesis and are only expressed during the G1 and S phases of the cell cycle. These enzymes allow herpes simplex virus replication in quiescent cells, so if they are inactivated by mutation the herpes simplex virus will only be able to replicate in proliferating cells, such as cancer cells. The G207 herpes simplex virus mutant contains a LacZ insertion, inactivating ribonucleotide reductase, as well as deletion of a virulence gene for safeties sake, has progressed to clinical trials for the treatment if brain cancer. The herpes simplex virus (HSV) (also known as Cold Sore, Night Fever, or Fever Blister) is a virus that manifests itself in two common viral infections, each marked by painful, watery blisters in the skin or mucous membranes (such as the mouth or lips) or on the genitals. ... In biology the genome of an organism is the whole hereditary information of an organism that is encoded in the DNA (or, for some viruses, RNA). ... DNA replication. ... The cell cycle, or cell-division cycle (CDC), is the cycle of events in a eukaryotic cell from one cell division to the next. ... Neuraminidase ribbon diagram An enzyme (in Greek en = in and zyme = blend) is a protein, or protein complex, that catalyzes a chemical reaction and also controls the 3D orientation of the catalyzed substrates. ... The herpes simplex virus (HSV) (also known as Cold Sore, Night Fever, or Fever Blister) is a virus that manifests itself in two common viral infections, each marked by painful, watery blisters in the skin or mucous membranes (such as the mouth or lips) or on the genitals. ... In cell biology, quiescence is the state of cell when it is not dividing. ... The herpes simplex virus (HSV) (also known as Cold Sore, Night Fever, or Fever Blister) is a virus that manifests itself in two common viral infections, each marked by painful, watery blisters in the skin or mucous membranes (such as the mouth or lips) or on the genitals. ... When normal cells are damaged or old they undergo apoptosis; cancer cells, however, avoid apoptosis. ... The herpes simplex virus (HSV) (also known as Cold Sore, Night Fever, or Fever Blister) is a virus that manifests itself in two common viral infections, each marked by painful, watery blisters in the skin or mucous membranes (such as the mouth or lips) or on the genitals. ... Virulence is a term used to refer to either the relative pathogenicity or the relative ability to do damage to the host of an infectious agent. ... In medicine, a clinical trial (synonyms: clinical studies, research protocols, medical research) is a research study. ... A brain tumor is any mass created by an abnormal and uncontrolled growth of cells either found in the brain (neurons, glial cells, epithelial cells, myelin producing cells, etc. ...


Poliovirus

Poliovirus is a natural neuropathogen, making it the obvious choice for selective replication in tumours derived from neuronal cells. Poliovirus has a plus-strand RNA genome, the translation of which depends on a tissue specific internal ribosomal entry site (IRES) within the 5' untranslated region of the viral genome, which is active in cells of neuronal origin and allows translation of the viral genome without a 5’ cap. Gromeier et al (2000) replaced the normal poliovirus IRES with a rhinovirus IRES, altering tissue specificity. The resulting PV1(RIPO) virus was able to selectively destroy malignant glioma cells, while leaving normal neuronal cells untouched. Poliomyelitis (polio) is a viral paralytic disease. ... Poliomyelitis (polio) is a viral paralytic disease. ... In biology the genome of an organism is the whole hereditary information of an organism that is encoded in the DNA (or, for some viruses, RNA). ... Look up translate in Wiktionary, the free dictionary. ... In biology the genome of an organism is the whole hereditary information of an organism that is encoded in the DNA (or, for some viruses, RNA). ... In biology the genome of an organism is the whole hereditary information of an organism that is encoded in the DNA (or, for some viruses, RNA). ... Species Human rhinovirus A (HRV-A) Human rhinovirus B (HRV-B) Rhinovirus (from the Greek rhin-, which means nose) is a genus of the Picornaviridae family of viruses. ...


Double Targeting

It is unlikely to be possible to make a virus entirely specific toward any tissue type by using just one form of targeting. Infection of normal tissue can result in adverse side effects. Double targeting with both transductional and non-transductional targeting methods is more effective than any one form of targeting alone. Davydova et al (2004) combined transductional targeting with a tumour-specific promoter to successfully target an adenovirus against Oesophageal Adenocarcinoma. Orders A virus is a submicroscopic particle that can infect the cells of a biological organism. ... In genetics, a promoter is a DNA sequence that enables a gene to be transcribed. ... Genera Mastadenovirus Aviadenovirus Atadenovirus Siadenovirus Adenoviruses are viruses of the family Adenoviridae. ...


Bystander effect

Tumour-selective replication-competent viruses can infect and lyse cancer cells, rapidly destroying them without the need for the expression of foreign genes. Viral replication also leads to local dose amplification and improved tumour penetration. However, their intrinsic ability to lyse tumour cells can be complimented by other mechanisms that increase the anti-tumour toxicity if the virus, so it is not necessary for all cells in the tumour to be infected and lysed. Orders A virus is a submicroscopic particle that can infect the cells of a biological organism. ... When normal cells are damaged or old they undergo apoptosis; cancer cells, however, avoid apoptosis. ... This stylistic schematic diagram shows a gene in relation to the double helix structure of DNA and to a chromosome (right). ... Orders A virus is a submicroscopic particle that can infect the cells of a biological organism. ...


Suicide Genes

Viruses can be used as vectors for delivery of suicide genes, encoding enzymes that can metabolise a separately administered non-toxic pro-drug into a potent cytotoxin, which can diffuse to and kill neighbouring cells. One herpes simplex virus, encoding a thymidine kinase suicide gene, has progressed to phase III clinical trials. The herpes simplex virus thymidine kinase phosphorylates the pro-drug, ganciclovir, which is then incorporated into DNA, blocking DNA synthesis. The tumour selectivity of oncolytic viruses ensures that the suicide genes are only expressed in cancer cells. Orders A virus is a submicroscopic particle that can infect the cells of a biological organism. ... Ribbon diagram of the enzyme TIM. TIM is catalytically perfect, meaning its conversion rate is limited, or nearly limited to its substrate diffusion rate. ... A prodrug is a pharmacological substance (drug) which is administered in an inactive (or significantly less active) form. ... As citotoxinas sao umas cenas que matam as células. ... The herpes simplex virus (HSV) (also known as Cold Sore, Night Fever, or Fever Blister) is a virus that manifests itself in two common viral infections, each marked by painful, watery blisters in the skin or mucous membranes (such as the mouth or lips) or on the genitals. ... In medicine, a clinical trial (synonyms: clinical studies, research protocols, medical research) is a research study. ... The herpes simplex virus (HSV) (also known as Cold Sore, Night Fever, or Fever Blister) is a virus that manifests itself in two common viral infections, each marked by painful, watery blisters in the skin or mucous membranes (such as the mouth or lips) or on the genitals. ... A prodrug is a pharmacological substance (drug) which is administered in an inactive (or significantly less active) form. ... The general structure of a section of DNA Deoxyribonucleic acid (DNA) is a nucleic acid —usually in the form of a double helix— that contains the genetic instructions specifying the biological development of all cellular forms of life, and most viruses. ... DNA replication. ... When normal cells are damaged or old they undergo apoptosis; cancer cells, however, avoid apoptosis. ...


Suppression of Angiogenesis

Angiogenesis (blood vessel formation) is an essential part of the formation of large tumour masses. Angiogenesis can be inhibited by the expression of several genes, which can be delivered to cancer cells in viral vectors, resulting in suppression of angiogenesis, and oxygen starvation in the tumour. The infection of cells with viruses containing the genes for angiostatin and endostatin synthesis inhibited tumour growth in mice. Angiogenesis is the physiological process involving the growth of new blood vessels from pre-existing vessels. ... Angiogenesis is the physiological process involving the growth of new blood vessels from pre-existing vessels. ... This stylistic schematic diagram shows a gene in relation to the double helix structure of DNA and to a chromosome (right). ... When normal cells are damaged or old they undergo apoptosis; cancer cells, however, avoid apoptosis. ... Angiogenesis is the physiological process involving the growth of new blood vessels from pre-existing vessels. ... A common alternate meaning of virus is computer virus. ... This stylistic schematic diagram shows a gene in relation to the double helix structure of DNA and to a chromosome (right). ...


Immune Response

In a number of cases, cancer cells exposed to viruses have experienced widespread necrosis, which cannot be entirely accounted for by viral replication alone. Cytotoxic T-cell responses directed against virus-infected cells have been identified as a important factor in tumour necrosis. However, since viruses are normal human pathogens, they induce an immune response, which reduces the effectiveness of viruses. For example, increased antibody titers could deactivate viruses before the tumour has been destroyed. This can be overcome by using parental viruses that are not normal human pathogens, thereby avoiding any pre-existing immunity. However, this does not avoid subsequent antibody generation. Alternatively, the viral vector can be coated with a polymer such as polyethylene glycol, shielding it from antibodies, but this also prevents viral coat proteins adhering to host cells. Deactivation of the immune system is not desirable, since it has a positive effect on tumour necrosis. When normal cells are damaged or old they undergo apoptosis; cancer cells, however, avoid apoptosis. ... T cells are a subset of lymphocytes that play a large role in the immune response. ... A request has been made on Wikipedia for this article to be deleted in accordance with the deletion policy. ... Schematic of antibody binding to an antigen An antibody is a protein used by the immune system to identify and neutralize foreign objects like bacteria and viruses. ... Schematic of antibody binding to an antigen An antibody is a protein used by the immune system to identify and neutralize foreign objects like bacteria and viruses. ... Polymer is a term used to describe a very long molecule consisting of structural units and repeating units connected by covalent chemical bonds. ... The immune system is the system of specialized cells and organs that protect an organism from outside biological influences. ...


Oncolytic Viruses in conjunction with existing cancer therapies

Chen et al (2001) used CV706, a prostate-specific adenovirus, in conjunction with radiotherapy on prostate cancer in mice. The combined treatment resulted in a synergistic increase in cell death, as well as a significant increase in viral burst size (the number of virus particles released from each cell lysis). No alteration in viral specificity was observed. Genera Mastadenovirus Aviadenovirus Atadenovirus Siadenovirus Adenoviruses are viruses of the family Adenoviridae. ... Radiation therapy (or radiotherapy) is the medical use of ionizing radiation as part of cancer treatment to control malignant cells (not to be confused with radiology, the use of radiation in medical imaging and diagnosis). ... Prostate cancer is a disease in which cancer develops in the prostate, a gland in the male reproductive system. ...


ONYX-015 has undergone trials in conjunction with chemotherapy. The combined treatment gave a greater response than either treatment alone, but the results have not been entirely conclusive. ONYX-015 has shown promise in conjunction with radiotherapy. Chemotherapy is the use of chemical substances to treat disease. ... Radiation therapy (or radiotherapy) is the medical use of ionizing radiation as part of cancer treatment to control malignant cells (not to be confused with radiology, the use of radiation in medical imaging and diagnosis). ...


Possible Applications

Virus gene therapy has never been used successfully against cancer, mainly due to poor transduction of cells. This problem is solved by oncolytic viruses. The use of viral agents to treat cancer is now a real possibility, and several very promising advances have been made e.g. ONYX-015. Orders A virus is a submicroscopic particle that can infect the cells of a biological organism. ... Bold textMedia:Example. ...


Viral agents administered intravenously can be particularly effective against metastatic cancers, which are especially difficult to treat conventionally. However, blood born viruses can be deactivated by antibodies and cleared from the blood stream quickly e.g. by Kupffer cells (extremely active phagocytic cells in the liver, which are responsible for adenovirus clearance). Avoidance of the immune system until the tumour is destroyed could be the biggest obstacle to the success of oncolytic virus therapy. To date, no techniques used seem to evade the immune system is entirely satisfactorily. It is in conjunction with conventional cancer therapies that oncolytic viruses show the most promise, since combined therapies operate synergistically with no apparent negative effects. An intravenous drip in a hospital Intravenous therapy or IV therapy is the administration of liquid substances directly into a vein. ... Metastasis (Greek: change of the state) is the spread of cancer from its primary site to other places in the body. ... Wikipedia does not yet have an article with this exact name. ... Kupffer cells are reticulendothelial cells located in the liver. ... Phagocytosis (literally cell-eating) is a form of endocytosis wherein large particles are enveloped by the cell membrane of a (usually larger) cell and internalized to form a phagosome, or food vacuole. ... The liver is the largest internal organ of the human body. ... Genera Mastadenovirus Aviadenovirus Atadenovirus Siadenovirus Adenoviruses are viruses of the family Adenoviridae. ... The immune system is the system of specialized cells and organs that protect an organism from outside biological influences. ... The immune system is the system of specialized cells and organs that protect an organism from outside biological influences. ...


The specificity and flexibility of oncolytic viruses means they have the potential to treat a wide range of cancers with minimal side effects. Oncolytic viruses have the potential to solve the problem of selectively killing cancer cells. However, altering the host range or tissue specificity of any virus has extremely serious safety implications. Nonetheless, the increasing understanding of viral replication mechanisms and the immune system means the effective treatment of cancer with virotherapy could be just around the corner. Side-effect can mean: Side-effect (computer science), a state change caused by a function call Adverse drug reaction, an unintended consequence specifically arising from drug therapy Therapeutic effect (medicine), a desirable consequence of any kind of medical treatment, even though resulting as an unintended, unexpected consequence of the treatment... When normal cells are damaged or old they undergo apoptosis; cancer cells, however, avoid apoptosis. ... Orders A virus is a submicroscopic particle that can infect the cells of a biological organism. ... Replication may mean: In biology: Self-replication, when a molecule (or any other pattern) makes a copy of itself DNA replication, the act of copying the genetic material of a cell (DNA) to a daughter cell Semiconservative replication, mechanism of DNA replication Other: replication (computer science), the provision of redundant... The immune system is the system of specialized cells and organs that protect an organism from outside biological influences. ... Introduction Virotherapy is a new, experimental form of cancer treatment using biotechnology to convert once-harmful viruses into cancer-fighting agents, by reprogramming viruses to only attack cancerous cells, while healthy cells can still easily ward them off. ...


External Links

  • www.ONYX-Pharm.com

Referenced Papers

  • Li Y, Pong R, Bergelson JM, Hall MC, Sagalowsky AI, Tseng C, Wang Z & Hsieh J; Loss of Adenoviral Receptor Expression in Human Bladder Cancer Cells: A Potential Impact on the Efficacy of Gene Therapy, Cancer Research, 59, 325-330 (1999)
  • Wickham TJ; Ligand-directed targeting of genes to the site of disease, Nature Medical, 9, 135-139 (2003)
  • Davydova J, Long PL, Gavrikova T, Wang M, Krasnykh V & Yamamoto M; Infectivity-Enhanced Cyclooxygenase-2-Based Conditionally Replicative Adenoviruses for Esophageal Adenocarcinoma Treatment, Cancer Research, 64, 4319-4327 (2004)
  • Rodriguez R, Schuur ER, Lim HY, Henderson GA, Simons JW & Henderson DR; Prostate attenuated replication competent adenovirus (ARCA) CN706: a selective cytotoxic for prostate-specific antigen-positive prostate cancer cells, Cancer Research, 57, 2559-2560 (1997)
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