{"id":21003,"date":"2018-06-25T10:48:14","date_gmt":"2018-06-25T10:48:14","guid":{"rendered":"http:\/\/biomedpharmajournal.org\/?p=21003"},"modified":"2018-10-05T07:14:32","modified_gmt":"2018-10-05T07:14:32","slug":"potential-of-genetically-modified-measles-virus-as-a-treatment-modality-for-carcinoma-a-review","status":"publish","type":"post","link":"https:\/\/biomedpharmajournal.org\/staging\/vol11no2\/potential-of-genetically-modified-measles-virus-as-a-treatment-modality-for-carcinoma-a-review\/","title":{"rendered":"Potential of Genetically- Modified Measles Virus As A Treatment Modality for Carcinoma \u2013 A Review"},"content":{"rendered":"

Introduction<\/strong><\/p>\n

For more than a century, viruses have been considered as potent experimental agents to eliminate or regress neoplastic growths.1<\/sup> A clear perspective about viruses increased in the 1950s and 1960s, immensely due to the development of cell and tissue culture systems which allowed vivo virus breeding.2,3\u00a0<\/sup>An early approach for the cure of cancer was through a toxin commonly known as the Colley\u2019s toxin. The toxin contained killed bacteria and proteins. Though Colley\u2019s toxin was not proven to be beneficial.4<\/sup> Later scientist tried to use infectious agents for the cure of cancer. In 1950\u2019s it was noticed that West Nile virus had tumour shrinking properties. West Nile virus had the risk of causing or developing a disease which is known as West Nile encephalitis. Therefore clinical trials had to come to an end. The history of oncolytic virotheraphy dates back to the 12th<\/sup> century that documented spontaneous regression of haematological cancers after wild measles infection. Over\u00a0 the past fifty years, viruses have been investigated wiintensity and their \u00a0biology is now appreciated more comprehensively than that of any other organism in nature. These efforts have led to better understanding of genomes and proteins, their physical structures, their replication cycles and pathogenetic strategies futher the ability to regulate\u00a0 their genomes have been deviced.5<\/sup> After constant research, oncolytic viruses were engineered. Various types of viruses like herpes virus, influenza virus, pox virus are being tested for their oncolytic properties.6 <\/sup>\u00a0The oldest vaccine used for the eradication of small pox is being researched for its oncolytic properties.7<\/sup> The modernised rein of oncolytic virotherapy, in which virus genomes are tailored\u00a0 to enhance their anti-tumor specificity, can be traced to a 1991 publication in which a thymidine kinase (TK)-negative herpes simplex virus (HSV) with attenuated neurovirulence was shown to be active in a murine.7\u00a0<\/sup>Presently the most cumbersome task is to find out the right kind of virus for destruction of particular type of tumour cells. Recently the cure of multiple myeloma was brought about by injecting genetically modified variants of measles virus. This progress brought the field of oncolytic virotheraphy into lime light.<\/p>\n

Oncolytic Virotheraphy<\/strong><\/p>\n

Viruses can specifically infect and lyse the tumour cells.8<\/sup> The basis for oncolysis rests on the below factors.<\/p>\n

Wild strains that affect the cancer cells.<\/p>\n

Attenuated mutants of human virus strains.<\/p>\n

Viruses attenuated by culturing techniques.<\/p>\n

The viral genes perform as tumour toxic agents and the capsids acts as vehicles.8\u00a0<\/sup>Oncolytic virus acquire\u00a0 their distinctive feature either by exploiting the cell surface receptors or intracellular gene aberration which are over expressed in cancer cells.8<\/sup> One of the greatest advantages of oncolytic virotheraphy is the ability to engineer the virus according to the outcomes of clinical trials. Cancer cells show altered cell physiology like insensitivity to inhibitory growth signals, extensive replicative potential, tissue invasion and metastatis and sustained angiogenisis. These alterations in cell physiology make selective replication of the virus possible.9<\/sup> Cancer targeting techniques of virus can be achieved by two approaches either by deleting the viral genes required for virus replication in normal cells or by using tumour specific promoters for viral genes.10\u00a0<\/sup>Experimentts performed with other oncolytic virus like reovirus and herpes virus exhibit\u00a0 that cyclophosphamide decrease the innate immune responses,\u00a0 extend viral gene expression and proliferation, and improve oncolytic effect. Alternate mechanisms to target cancer cells is to distinctively erase off\u00a0 the\u00a0 undesirable tropism. This is achieved by specifically constructing the virus for various specified target organs in their genomes to facilitate the selective blocking of the virus\u2019s\u00a0 life cycle\u00a0 in the target organs like brain, liver , muscle specific micro RNA. Another\u00a0 method is to alter the\u00a0 viruses\u00a0 so as to produce\u00a0 immune\u2013stimulating chemicals.<\/p>\n

Cure for Multiple Myeloma<\/strong><\/p>\n

A clinical trial at the Mayo Clinic suggests that a altered\u00a0 version of the measles virus could be used to aim at the \u00a0cancer cells and put the condition into absolution. Scientist\u00a0 intravenously administered 10,000 times the typical dosage of measles vaccine to two women, 49- and 65-years-old, who had multiple myeloma, an unusual cancer affecting white blood cells in bone marrow. The virus, that was modified to target cancer cells, eiminated or reduced tumours in the two patients. .In addition to multiple myeloma trial, the modified measles virus is being tested in glioblastoma multiforme (brain cancer) and ovarian cancer.11 <\/sup>\u00a0The measles virus was genetically modified to contain mammalian NIS gene. On injecting the modified variants of the virus, the tumour cells are bestowed with the capacity to concentrate radioactive iodine i.e. the gene contains information that enables the of iodine from the blood stream to the tumour cells.11<\/sup>\u00a0 The presence of radioactive iodine within the tumour cells enables easy tracing of the malignant cells with the help of iodine markers.After injecting measles, the patients \u00a0suffered from short lived symptoms like fever, low blood pressure and also rapid heart attack.<\/p>\n

The over expression of CD46 by the malignant plasma cells(myeloma cells) makes it a target of choice for the measles virus .In short the life cycle of measles virus complements that of myeloma cells. Genetically modified virus gains access to the bone marrow by infecting the RES. The viruses seek and destroy the tumour by multiplying within the tumour cells. The oncolytic effect of the MV-NIS strain can be augmented by administering the \u03b2 and \u03b3 emitter .IMV strains can be retargeted to display a\u00a0 ligands such asepidermal growth factor receptor vIII, single-chain antibodies against epidermal growth factor receptor, epidermal growth factor receptor vIII, CD38, 30 Her-2\/neu, 28 folate receptor \u03b1,\u00a0 31 CD20, 24 and cytokines such as interleukin, targeting receptors highly expressed in tumour cells . An important challenge in the development of MVstrains as cancer therapeutics is preclinical toxicology testing because of the significant limitations of existing animal models as rodents expression of the MV receptors CD46 and SLAMis nil.\u00a0 Toxicology studies by IV administration of MV-NIS virus was done in cynomolgus monkeys.<\/p>\n

Mechanism of Oncolysis<\/strong><\/p>\n

Negative strand RNA paramyxovirus is measles virus. It contains 6 genes that encode 8 proteins, the proteins being<\/p>\n

Nucleocapsid (N)<\/p>\n

Fusion (F)<\/p>\n

Haemagglutinin (H)<\/p>\n

Matrix(M)<\/p>\n

Large proteins (L)\u00a0 and small proteins (C and V)<\/p>\n

Phospho (P)<\/p>\n

The viruses enter the cell by pH independent membrane fusion. The\u00a0 membrane and receptorfusion takes place which is initiated by F and H proteins respectively. Interaction betweentworeceptor present in the cancer cells namely CD46 and signalling lymphocyte activation system (SLAS) and the H protein takes place. The expression of CD46 helps the tumour cells to escape apoptosis as the cells protect themselves from complement activated lysis. After the process of receptor recognition by the H protein changes of F protein leading to fission and viral entry occur.12<\/sup> Therefore typical cytophatic effects of measles virus are due to the formation of gaint mononuclear cell aggregates. The production of syncytia can\u00a0 greatly uplift\u00a0 the antitumor effect of the virus because, for every infected cell, 50\u2013100 neighbouring cells can\u00a0 fuse and sanctais formed which is\u00a0 followed by apoptosis. The derivates of measles virus are tumour specific and has minimal cytophatic effects on non-transformed and normal cells. Measles virus infection\u00a0 is said to cause profound immunosuppression,\u00a0 thereby \u00a0making\u00a0 the patients susceptible to secondary infections which inturn accounts\u00a0 accounts\u00a0 for high mortality and morbidity. The vaccine strains\u00a0 and Edmonston strain of measles virus obtained from it is used like a cellular receptor human CD46 but most clinical isolates of measles virus cannot use CD46 as a receptor-5. Transfection with a human SLAM (signalling lymphocyte-activation molecule; also known as CDw150) complementary DNA enables non-susceptible cell lines to combine measles virus and supports measles virus replication and develop cytopathic effects.<\/p>\n

The diffusion of SLAM on various cell lines is consistent with their susceptibility to clinical isolates of measles virus. The identification of SLAM as a receptor for measles virus opens the way to a better comprehension of the pathogenesis of measles virus infection, especially the immunosuppression induced by measles virus.13<\/sup><\/p>\n

The current strategies in oncolytic virotherapy are as follows<\/p>\n

Overriding\u00a0 of innate immune response enhances efficacy<\/p>\n

Carrier cell technique avoids immune attack<\/p>\n

Addressing tumor microenvironment enhances viral spread and efficacy<\/p>\n

Oncolytic viruses destroy cancer stem cells<\/p>\n

Genetic engineering of oncolytic viruses complements<\/p>\n

chemo-and molecular-targeted therapies<\/p>\n

Genetic engineering of oncolytic viruses aims cancer signaling pathways<\/p>\n

Unique oncolytic virus species are being explored,<\/p>\n

Clinical trials <\/strong><\/p>\n

Overriding\u00a0 innate immune response enhances efficacy <\/strong><\/p>\n

The interaction between\u00a0 virus-immune system\u00a0 have been greatly pondered in relation to virotherapy. Innate immune responses to the virus is a prime obstrucle\u00a0 for long-term gene expression and oncolytic potency. The adoption of immunomodulatory agents in coherence\u00a0 with oncolytic viruses was first reported in the 1970s . Various studies\u00a0 demonstrate the\u00a0 efficacy of\u00a0 cyclophosphamide to inhibit regulatory T cells\u00a0 induction, neutralizing antibody induction, macrophages, regulatory T cells\u00a0 induction and intra-tumoral interferon(IFN)-g production.Though suppression of\u00a0 immune system enhances the effectiveness\u00a0 of\u00a0 the treatment and thereby influencing the overall prognosis to a great extent, it is yet\u00a0 to be determined ,if\u00a0 this strategy\u00a0\u00a0 would\u00a0 be beneficial\u00a0 in\u00a0 patients with\u00a0 varying\u00a0 degree of\u00a0 previously present \u00a0\u00a0immunosuppression.<\/p>\n

Carrier Cell Strategy<\/strong><\/p>\n

By\u00a0 preventing\u00a0 the immune\u00a0 responses one can take exploit the immune system to upgrade antitumor responses. Cytokine-induced killer (CIK) cells destroy tumor cells . After segregating\u00a0 the CIK cells from mice, these cells were infected with oncolytic vaccines viruses and re \u2013administered\u00a0 into animals with tumors.\u00a0 Hence considerably\u00a0 larger amounts of oncolytic viruses were transported to the tumor. Therefore it was\u00a0 noted\u00a0 that both the oncolytic viruses and CIK cells were coherent in tumor killing(12).A\u00a0 drawback of this approach\u00a0 is that\u00a0 it demands harvesting of cells from specific patients, ex vivo nurturing\u00a0 and re- introduction to the patients and thereby requiring\u00a0 a substantial amount of laboratory work. Never the less , this approach\u00a0 holds promise in\u00a0 expanding the\u00a0\u00a0 potency of\u00a0 the\u00a0 approach.<\/p>\n

Addressing\u00a0 the Tumor Microenvironment Enhances Viralspread And Efficacy<\/strong><\/p>\n

Tumor microenvironment plays a pivotal\u00a0 role in limiting\u00a0 viral spread and enhancing \u00a0tumor growth\u00a0 various approaches have been taken. Coadministration of matrix modifying agents (bacterial collagenase, MMP-1, 8) has demonstrated\u00a0 to augment\u00a0\u00a0 the spread of oncolytic HSV,24,25 although concerns regarding\u00a0 tumor metastases have to be scrutinized in more preclinical models before translation into clinical trials(13). Tumor hypoxia and its impact on viral replication have also been studied. Inflammation induced by virus infection impacts\u00a0 the tumor microenvironment. Pretreatment with cyclophosphamide subdued the inflammation and culminated\u00a0 in decreased tumor vascular permeability.14<\/sup> Kirn et al.showed that systemically administered vaccinia virus resulted in infection and subsequent destruction of tumor endothelial cells, which led to loss of tumor vascular density.\u00a0 The efficacy of virotherapy can be limiting when replication-mediated oncolysis is the sole MOA.<\/p>\n

Oncolytic Viruses Destroy\u00a0 Cancer Stem Cells<\/strong><\/p>\n

From the latest explorations in the field of cancer stemcells, it\u00a0 has\u00a0 become\u00a0 evident\u00a0 that the neoplastic\u00a0 cell community\u00a0 not only induce\u00a0 tumorigenesis, but also contribute\u00a0 towards resistance to chemo- and radiation therapy.15<\/sup> As these cell populations\u00a0 replicatie and self renewl, oncolytic viruses that are constructed\u00a0 to target cell cycle-dysregulated tumor cells might also possess the potential\u00a0 to\u00a0 destroy cancer stem cells. The\u00a0 mechanism of\u00a0 action would\u00a0 incorporate\u00a0 replication-induced cell annhilation otherwise known as\u00a0 necrosis and autophagy\u00a0 that is degradation of intracellular components in lysosomes.<\/p>\n

Genetic Engineering<\/strong><\/p>\n

Genetic engineering of oncolytic viruses complementschemo- and molecular-targeted therapie of of the viruses allows functional complementation to chemotherapeutic agents and molecular-targeted therapeutics.15<\/sup><\/p>\n

Ideal Oncolytic Virus Species are Being Explored<\/strong><\/p>\n

As majority of\u00a0 oncolytic viruses have\u00a0 exhibited less than optimal efficiency\u00a0 in clinical trials as solitary agents, there is utmost interest in exploring novel viral species. These studies assess oncolytic activity and \u00a0investigate tumor selectivity.<\/p>\n

A large number of Clinical Trials have been Carried out<\/strong><\/p>\n

Virotherapy has\u00a0 an array of features that are unique from\u00a0 other remedies. Its diverse\u00a0 innovative MOAs incorporate replication-mediated oncolysis,antitumoral immunity induction, antiangiogenesis, apoptosis and autophage induction. There is no cross resistance with other treatment modalities\u00a0 and synergistic interaction is exhibited\u00a0 with other treatment regime. Safety in human has been demonstrated in more than 800 patients.16<\/sup><\/p>\n

Current Trends and Scope of Oncolytic Virotherapy<\/strong><\/p>\n

Although a spectrum\u00a0 of therapeutic options for\u00a0 battling neoplasms\u00a0 inclusive of\u00a0 surgery, chemotherapy, and local ablative therapies are available, the prognosis for major malignancies remains merger with a median years or months\u00a0 of\u00a0 survival. Inspite of marked progress in recent years, most advanced malignancies remain incurable and hence there is an immediate need for the development of novel therapeutics.17<\/sup> Inspite of exploration of various therapeutic alternates, namely hormonal therapy, immunotherapy, and gene therapy the complete cure for the neoplasms remains a true challenge. The current approach for the treatment\u00a0 of malignancies is gene therapy, to use viral and non-viral gene therapy systems.18 Gene-based therapeutics has considerable promise as a treat modality. Though gene therapy was originally perceived\u00a0 as a strategy for treating monogenic diseases, its scope has eventually broadened to incorporate\u00a0 the in vivo<\/em> expression of foreign gene products that can produce\u00a0 tumor cell lysis.19<\/sup><\/p>\n

The efficacy of new generation oncolytic virus is one of the key issues. Increase in anti \u2013tumour activity is being brought about either by incorporating suside genes in the genome or by transiently suppressing the immunity for viral infections. These methods apart from increasing the efficacy also increase the toxicity.19<\/sup> Higher risks of viral replication are present with immune suppression. This modality of treatment needs a lot of research as there are no proven ways to monitor the in-vivo spread, elimination and for the measurement of viral gene expression and kinetics.20<\/sup> Cyclophosphamide, a novel strategy is currently being refined\u00a0 to bypass antimeasles immunity and accelerate systemic delivery in future applications of this technology . One among these notions comprises\u00a0 the use of cell carriers such as monocytoid cell lines or mesenchymal stem cells, which could protect MV from the immune system, transfer the virus, and efficiently deliver it to tumour cells.21<\/sup> Intravenously administered viruses are promptly washed off\u00a0 from the circulation as a result of sequestration by the mononuclear phagocyte system in the liver and spleen.\u00a0 Prior to clearance, they are opsonised with antibodies, complements, coagulation factors and other serum proteins that enhance their recognition by splenic macrophages and hepatic Kupffer cells. These fragments combine with the\u00a0 receptors like Fc\u03b3 receptors, complement receptor 1 (CR1), CR3 or scavenger receptors on macrophages and endothelial cells, culminating in receptor-mediated phagocytosis and elevated clearance from the circulation.14<\/sup> \u00a0An approach to curtail sequestration include chemical alterations of the surface proteins of the viruses by association\u00a0 of biocompatible polymers, such as polyethylene glycol.<\/p>\n

Conclusion<\/strong><\/p>\n

Oncolytic virotheraphy is an emerging field of\u00a0 cancer biology\u00a0\u00a0 that needs\u00a0 improvement for\u00a0 implementation as\u00a0 sole treatment option for cancer.\u00a0 Logical designing of the viruses based on the knowledge in virology would help to deliver the\u00a0 virus to the tumour site much effectively with reduced side effects.22<\/sup> Ex \u2013vivo administration of viruses\u00a0 prior to\u00a0 administration to human beings is advised .\u00a0 Further a critical\u00a0 biological brink\u00a0 that has to be exhibited\u00a0 with all species of oncolytic virus is tumor-selective virus replication, therapeutic transgene expression and biological function.22,23<\/sup> \u00a0These developments in the method of treatment help to enhance the prognosis of the patient and also helps to reduce the mortality and morbidity rate due to cancer . The\u00a0 raising onset , the inadequacy\u00a0 of effective therapies, and the devastating prognosis of life threatening neoplasm support the immediate\u00a0 need for new therapeutic agents that are both safe and effective.24,25<\/sup> \u00a0These issues if addressed in a timely fashion\u00a0 and extended\u00a0 to clinical trials ,virotherapy\u00a0 will exhibit \u00a0great promise as an absolute\u00a0 treatment manifeston for malignancies with the edge of the potential lack of cross-resistance with standard therapies.<\/p>\n

Acknowledgement<\/strong><\/p>\n

The author(s) received no specific funding for this work.<\/p>\n

References<\/strong><\/p>\n

    \n
  1. Kelly E, Russell S.J. History of oncolytic viruses: genesis to genetic engineering. Molecular Therapy<\/em>. 2007;1;15(7):651-9.<\/li>\n
  2. Gey \u00a0G. Tissue culture studies of the proliferative capacity of cervical carcinoma and normal epithelium. Cancer Res<\/em>. 1952;12:264-5.<\/li>\n
  3. Weller T.H, Robbins F.C, Enders J.F. Cultivation of poliomyelitis virus in cultures of human foreskin and embryonic tissues. Proceedings of the Society for Experimental Biology and Medicine.<\/em> 1949;72(1):153-5
    \nCrossRef<\/a><\/li>\n
  4. Cripe T.P, Wang P.Y, Marcato P, Mahller Y.Y, \u00a0Lee PW. Targeting cancer-initiating cells with oncolytic viruses. Molecular Therapy<\/em>. 2009;1;17(8):1677-8.<\/li>\n
  5. Cattaneo R, Miest T, Shashkova E.V, Barry M.A. Reprogrammed viruses as cancer therapeutics: targeted, armed and shielded. Nature Reviews Microbiology<\/em>. 2008; 1;6(6):529-40.<\/li>\n
  6. Betancourt D.M. Vesicular Stomatitis Virus is a Malleable Oncolytic Vector for the Treatment of Various Malignancies<\/em>(Doctoral dissertation, University of Miami).<\/li>\n
  7. Singh P.K, Doley J, Kumar G.R, Sahoo A.P, Tiwari A.K. Oncolytic viruses & their specific targeting to tumour cells. The Indian journal of medical research<\/em>. 2012;136(7):571.<\/li>\n
  8. Galanis E. Therapeutic potential of oncolytic measles virus: promises and challenges. Clinical Pharmacology & Therapeutics<\/em>. 2010;1;88(7):620-5.<\/li>\n
  9. Tatsuo H, Ono N, Tanaka K, Yanagi Y. SLAM (CDw150) is a cellular receptor for measles virus. Nature. 2000;406(6798):893.
    \n    CrossRef<\/a><\/li>\n
  10. Fulci G, Breymann L, Gianni D, Kurozomi K, Rhee S.S, Yu J, Kaur B, Louis DN, Weissleder R, Caligiuri MA, Chiocca EA. Cyclophosphamide enhances glioma virotherapy by inhibiting innate immune responses. Proceedings of the National Academy of Sciences.<\/em> 2006;22;103(34):12873-8.<\/li>\n
  11. Qiao J, Wang H, Kottke T, White C, Twigger K, Diaz RM, Thompson J, Selby P, De Bono J, Melcher A, Pandha H. Cyclophosphamide facilitates antitumor efficacy against subcutaneous tumors following intravenous delivery of reovirus. Clinical Cancer Research.<\/em> 2008;1;14(1):259-69.<\/li>\n
  12. Francica J.R. A study of the Ebola virus glycoprotein: Disruption of host surface protein function and evasion of immune responses (Doctoral dissertation, University of Pennsylvania)<\/li>\n
  13. Duke T, Mgone C.S. Measles:not just another viral exanthem. The Lancet<\/em>. 2003;1;361(9359):763-73.<\/li>\n
  14. Lamfers M.L, Fulci G, Gianni D, Tang Y, Kurozumi K, Kaur B, Moeniralm S, Saeki Y, Carette JE, Weissleder R, Vandertop WP. Cyclophosphamide increases transgene expression mediated by an oncolytic adenovirus in glioma-bearing mice monitored by bioluminescence imaging. Molecular Therapy.<\/em> 2006;1;14(6):779-88.<\/li>\n
  15. Liu T.C, Kirn D. Gene therapy progress and prospects cancer: oncolytic viruses. Gene therapy<\/em>. 2008;15(12):877.
    \n    CrossRef<\/a><\/li>\n
  16. Fulci G, Dmitrieva N, Gianni D, Fontana E.J, Pan X, Lu Y, Kaufman C.S, Kaur B, Lawler S.E, Lee R.J, Marsh CB. Depletion of peripheral macrophages and brain microglia increases brain tumor titers of oncolytic viruses. Cancer research<\/em>. 2007;1;67(19):9398-406.<\/li>\n
  17. Li H, \u00a0Zeng Z, \u00a0Fu X, Zhang X. Coadministration of a Herpes simplex Virus-2\u2013based oncolytic virus and cyclophosphamide produces a synergistic antitumor effect and enhances tumor-specific immune responses. Cancer research.<\/em> 2007;15;67(16):7850-5.<\/li>\n
  18. Ungerechts G, Springfeld C, Frenzke ME, Lampe J, Parker WB, Sorscher EJ, Cattaneo R. An immunocompetent murine model for oncolysis with an armed and targeted measles virus. Molecular Therapy<\/em>. 2007;1;15(7):1991-7.<\/li>\n
  19. Di Paolo N.C, Tuve S, Ni S, Hellstr\u00f6m KE, Hellstr\u00f6m I, Lieber A. Effect of adenovirus-mediated heat shock protein expression and oncolysis in combination with low-dose cyclophosphamide treatment on antitumor immune responses. Cancer research<\/em>. 2006;15;66(2):960-9.<\/li>\n
  20. Liu T.C, Zhang T, Fukuhara H, Kuroda T, Todo T, Canron X, Bikfalvi A, Martuza RL, Kurtz A, Rabkin SD. Dominant-negative fibroblast growth factor receptor expression enhances antitumoral potency of oncolytic herpes simplex virus in neural tumors. Clinical cancer research. <\/em>2006;15;12(22):6791-9.<\/li>\n
  21. Liu T.C, Zhang T, Fukuhara H, Kuroda T, Todo T, Martuza R.L, \u00a0Rabkin S.D, Kurtz A. Oncolytic HSV armed with platelet factor 4, an antiangiogenic agent, shows enhanced efficacy. Molecular Therapy<\/em>. 2006;1;14(6):789-97<\/li>\n
  22. Power A.T, Bell J.C. Cell-based delivery of oncolytic viruses: a new strategic alliance for a biological strike against cancer. Molecular Therapy.<\/em> 2007;1;15(7):660-5.<\/li>\n
  23. Pasquinucci G. Possible effect of measles on leukaemia. The Lancet.<\/em> 1971;16;297(7690):136.<\/li>\n
  24. Bluming A, Ziegler J. Regression of Burkitt’s lymphoma in association with measles infection. The Lancet. 1971;10;298(7715):105-6.<\/li>\n
  25. Bell J.C. Taming measles virus to create an effective cancer therapeutic. InMayo Clinic Proceedings. \u00a0<\/em>2014;1;89;7;863-865). Elsevier.<\/li>\n
  26. P, Dispenzieri A, Galanis E. Clinical testing of engineered oncolytic measles virus strains in Msaouel the treatment of cancer: an overview. Current opinion in molecular therapeutics.<\/em> 2009;11(1):43.<\/li>\n
  27. Hutzen B, Bid H.K, Houghton P.J, Pierson C.R, Powell K, Bratasz A, Raffel C, Studebaker A.W. Treatment of medulloblastoma with oncolytic measles viruses expressing the angiogenesis inhibitors endostatin and angiostatin. BMC cancer<\/em>. 2014;14(1):206.
    \n    CrossRef<\/a><\/li>\n
  28. Cutts F.T, Markowitz L.E. Successes and failures in measles control. Journal of infectious diseases.<\/em> 1994;1;170(1):32-41.<\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"

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