Junction Adhesion Molecule Is a Receptor for Reovirus

Cell, Journal Year: 2001, Volume and Issue: 104(3), P. 441 - 451

Published: Feb. 1, 2001

Language: Английский

---

Oncolytic Virotherapy: A Contest between Apples and Oranges

Molecular Therapy, Journal Year: 2017, Volume and Issue: 25(5), P. 1107 - 1116

Published: April 7, 2017

Viruses can be engineered or adapted for selective propagation in neoplastic tissues and further modified therapeutic transgene expression to enhance their antitumor potency druggability. Oncolytic viruses (OVs) administered locally intravenously spread a variable degree at sites of tumor growth. OV-infected cells die situ, releasing viral antigens that are phagocytosed by macrophages, transported regional lymph nodes, presented antigen-reactive T cells, which proliferate before dispersing kill uninfected distant sites. Several OVs showing clinical promise, one them, talimogene laherparepvec (T-VEC), was recently granted marketing approval intratumoral therapy nonresectable metastatic melanoma. T-VEC also appears substantially responsiveness checkpoint inhibitor antibody therapy. Here, we examine the paradigm review some approaches currently being pursued develop next generation both local systemic administration, as well use combination with other immunomodulatory agents. virotherapy uses replication-competent have been amplify selectively growth.1Russell S.J. Peng K.W. Bell J.C. virotherapy.Nat. Biotechnol. 2012; 30: 658-670Crossref PubMed Scopus (973) Google Scholar, 2Seymour L.W. Fisher K.D. viruses: finally delivering.Br. J. Cancer. 2016; 114: 357-361Crossref (83) Scholar In situ killing infected either infection host immune system, creates inflammatory milieu containing all ingredients necessary boost immunity (Figure 1). The relative contributions these two modes cell (direct oncolysis boosted immunity) is heavily impacted neutralizing antibodies virus-reactive generated during previous virus exposures. Virus exposure history is, therefore, an important driver interindividual variability oncolytic (OV) responses, especially first dose administered, may lead progressive changes magnitude response each successive dose. Talimogene (T-VEC) herpes simplex type 1 (HSV-1) regulatory treatment inoperable malignant melanoma.3Rehman H. Silk A.W. Kane M.P. Kaufman H.L. Into clinic: first-in-class therapy.J. Immunother. 4: 53Crossref (229) 4Bommareddy P.K. Patel A. Hossain S. melanoma.Am. Clin. Dermatol. 2017; 18: 1-15Crossref (148) Administered intratumorally into more accessible (usually cutaneous) lesions every 2 weeks up 18 months, produced durable responses 16% treated patients,5Andtbacka R.H. Collichio F. Amatruda T. Senzer N. Chesney Delman K.A. Spitler L.E. Puzanov I. Agarwala S.S. et al.Talimogene improves rate patients advanced melanoma.J. Oncol. 2015; 33: 2780-2788Crossref (1608) has since shown extraordinarily promising activity same disease indication when combined ipilumumab pembrolizumab therapy.6Puzanov Milhem M.M. Minor D. Hamid O. Li Chen L. Chastain M. Gorski K.S. Anderson Chou ipilimumab previously untreated, unresectable stage IIIB-IV 34: 2619-2626Crossref (376) 7Long G.V. Dummer R. Ribas VanderWalde Andtbacka R.H.I. Michielin Olszanski A.J. Malvehy Cebon J.S. al.Efficacy analysis MASTERKEY-265 phase 1b study lapherparevec pembrolizuman (pembro) 34Google Efforts now underway explore potential across spectrum different cancers. Unsurprisingly, successful emergence FDA (Food Drug Administration)-approved drug accelerating commercial development efforts world having positive energizing effect on numerous academic groups early-stage companies working broad deriving from many families various ways. this article, commemorate 20th anniversary journal Molecular Therapy, will focus initially T-VEC, giving brief overview its origins, design, development, mechanism action. We then address three key assumptions driving sustaining current additional platforms. assumption not last word better come. second prove superior paradigm. third that, even if found, wider selection facilitate outcomes achieved alone; example, through sequential given patient selecting based specific characteristics his her tumor. Finally, discuss therapy, selection, OV veterinary practice, likely accelerate progress coming years. Our intent provide comprehensive field, apologize those investigators whose outstanding discussed. For coverage topics, interested reader referred number published reviews addressing early field,8Kelly E. Russell History genesis genetic engineering.Mol. Ther. 2007; 15: 651-659Abstract Full Text PDF (470) design construction viruses,9Maroun Muñoz-Alía Ammayappan Schulze K.-W. Designing building viruses.Future Virol. (Published online March 31, 2017)https://doi.org/10.2217/fvl-2016-0129Crossref (86) immunotherapy,10Keller B.A. viruses—immunotherapeutics rise.J. Mol. Med. (Berl.). 94: 979-991Crossref (42) experience date ongoing trials.11Lawler S.E. Speranza M.C. Cho C.F. Chiocca E.A. cancer treatment: review.JAMA July 21, 2016)https://doi.org/10.1001/jamaoncol.2016.2064Crossref (334) were definite 1950s.8Kelly Encouraged occasional case reports spontaneous regressions coincided illnesses, variety newly identified intentionally patients. Not infrequently, tumors regressed, but it remained unknown whether due direct amplified immunity. Whatever cause, erratic, short lived, sometimes associated unacceptable normal tissue toxicities (e.g., lethal encephalitis). Interest waned revived after 1989, Dr. Robert Martuza reported Science genetically HSV-1 thymidine kinase gene had inactivated led control without encephalitis intracerebral glioma mouse model.12Martuza R.L. Malick Markert J.M. Ruffner K.L. Coen D.M. Experimental human means mutant.Science. 1991; 252: 854-856Crossref (783) This landmark set renaissance continued day, manner specificity, safety, druggability, immunogenicity, potency. HSV attract considerable attention malleable platform tumor-selective variants generated. A favorite approach destroy neurovirulence lab-adapted strains disrupting copies γ-34.5 encoded protein normally suppresses antiviral cell. Without γ-34.5, unable shut down interferon (by suppressing TBK-1 [TANK-binding 1]), block PKR (protein R)-mediated shutoff synthesis cell, inhibit autophagy via beclin-1 blockade.13Wilcox D.R. Longnecker factor γ34.5: revealing virus-host interactions.PLoS Pathog. 12: e1005449Crossref (35) Some γ-34.5-deleted HSVs tested clinically, most notably patients, encouraging definitive results.14Kaur B. Cripe T.P. virotherapy: opportunities progress.Curr. Pharm. 13: 1842-1851Crossref (51) (or JS1/ICP34.5−/ICP47−/GM-CSF [granulocyte macrophage colony-stimulating factor], become known T-VEC) originally described 2003.15Liu B.L. Robinson Han Z.Q. Branston English C. Reay P. McGrath Y. Thomas S.K. Thornton Bullock al.ICP34.5 deleted enhanced oncolytic, stimulating, anti-tumour properties.Gene 2003; 10: 292-303Crossref (560) thinking behind lab-adapted, predecessors over-attenuated. Thus, derived fresh pathogenic isolate obtained cold sore lab worker. Although attenuated gene, attenuation partially reversed engineering US11, product blocks synthesis, expressed earlier cycle. addition de-attenuating modifications, effectively response. deleting ICP47 antigen presentation inserting GM-CSF activate promote differentiation resident antigen-presenting (APCs) rapidly clinic active melanoma, shrinking injected leading regression lesions.16Kaufman Kim D.W. DeRaffele G. Mitcham Coffin R.S. Kim-Schulze Local induced intralesional vaccination encoding IIIc IV melanoma.Ann. Surg. 2010; 17: 718-730Crossref (403) 3 registration trial launched May 2009, years approvals anti-CTLA4 B-raf vemurafenib. randomization arm subcutaneous GM-CSF, very little antimelanoma activity. Between 2009 2011, 436 (stage III IV) melanoma randomly assigned weeks. (responses lasting least 6 months) 16.3% 2.1% arm, longer overall survival 23.3 months versus 18.9 GM-CSF.5Andtbacka Based findings, biologics license application filed, U.S. October 2015, European Australian shortly thereafter. Arguably, ideal vaccine. It spreads within kills necroptosis, causing them release antigens, damage-associated molecular patterns (DAMPs), providing what possibly near-perfect environment activated APCs phagocytose mixture CD4+ helper CD8+ cytotoxic nodes.17Kohlhapp F.J. pathways: action laherparepvec, new immunotherapy.Clin. Cancer Res. 22: 1048-1054Crossref (188) Co-presentation individual "fed" virus-infected lysate greatly increases probability tumor-reactive lymphocytes (CTLs) recognizing tumor-specific MHC (major histocompatibility complex)-neoantigenic peptide complexes stimulated rich cytokines cells), increasing amplification, release, subsequent trafficking back growth, basis responses. Can improve upon this? Will alternative configurations T-VEC? There under matrix-degrading enzymes spread,18Hong C.S. Fellows W. Niranjan Alber Watkins Cohen J.B. Glorioso Grandi Ectopic matrix metalloproteinase-9 brain enhances vector infection.Gene 1200-1205Crossref (33) fusogenic membrane glycoproteins potency,19Nakamori Fu X. Meng Jin Tao Bast Jr., R.C. Zhang Effective ovarian incorporating fusion mechanisms.Clin. 9: 2727-2733PubMed 20Simpson G.R. Construction characterization glycoprotein prodrug activation control.Methods Biol. 2009; 542: 551-564Crossref (5) and/or receptor-targeted attachment proteins,21Menotti Cerretani Hengel Campadelli-Fiume fully retargeted recombinant capable entering solely epidermal growth receptor 2.J. 2008; 82: 10153-10161Crossref (91) 22Goins W.F. Hall Retargeting (HSV) vectors.Curr. Opin. 21: 93-101Crossref (18) microRNA targets,23Lee C.Y. Rennie P.S. Jia W.W. MicroRNA regulation virus-1 prostate cells.Clin. 5126-5135Crossref (87) 24Mazzacurati Marzulli Reinhart Miyagawa Uchida Goins Kaur Caligiuri al.Use miRNA sequences off-target replication increase safety unattenuated, glioblastoma-targeted HSV.Mol. 23: 99-107Abstract (57) tissue-specific promoters25Kambara Okano Saeki An mutant expressing ICP34.5 nestin promoter animals symptomatic tumor.Cancer 2005; 65: 2832-2839Crossref (179) 26Yoo J.Y. Haseley Bratasz Powell K. Antitumor efficacy 34.5ENVE: transcriptionally "Vstat120"-expressing virus.Mol. 20: 287-297Abstract (45) target tropisms. With tighter specificity targeted HSVs, considered reasonable de-attenuate reconstituting γ-34.5) restore newer T-VECs increased simply optimizing injection technique? What gained changing composition interleukins, cytokines, chemokines genome? engaged proteins cells? answers questions difficult predict model preclinically, but, judging intensity area present time, soon forthcoming. So about viruses? no only promise responds virotherapy. cancer, several families27Foreman P.M. Friedman G.K. Cassady glioma.Neurotherapeutics. 6, 2017)https://doi.org/10.1007/s13311-017-0516-0Crossref (96) results. Examples include poliovirus neuroattenuating rhinovirus internal ribosome entry site ([PV-RIPO] NCT: 01491893);28Goetz Dobrikova Shveygert Dobrikov Gromeier against glioma.Future 2011; 6: 1045-1058Crossref (38) C-type retrovirus enzyme cytosine deaminase, 5-fluorocytosine 5-fluorouracil (Toca-511);29Cloughesy T.F. Landolfi Hogan D.J. Bloomfield Carter C.C. Elder Kalkanis S.N. Kesari Lai al.Phase vocimagene amiretrorepvec recurrent high-grade glioma.Sci. Transl. 8: 341ra75Crossref (128) integrin-targeted serotype 5 adenovirus neuroattenuated E1A deletion (DNX-2401);30Lang Conrad Gomez-Manzano C.D. Tufaro Yung Sawaya Weinberg Prabhu Fuller Aldape Fueyo First-in-human I delta-24-RGD (DNX-2401) biological endpoints: Implications viro-immunotherapy.Neuro 2014; 16: iii39Crossref nonengineered rat parvovirus (H-1PV).31Geletneky Huesing Rommelaere Schlehofer J.R. Leuchs Dahm Krebs von Knebel Doeberitz Huber Hajda Phase I/IIa intratumoral/intracerebral intravenous/intracerebral administration Parvovirus H-1 (ParvOryx) primary glioblastoma multiforme: ParvOryx01 protocol.BMC 99Crossref (123) Also, non-brain-cancer indications, there examples following non-T-VEC oncolytics. Noteworthy H101, E1B-deleted approved Chinese 2005 head neck standard chemotherapy;32Xia Z.J. Chang J.H. Jiang W.Q. Guan Z.Z. Liu J.W. Hu X.H. Wu G.H. Wang H.Q. al.[Phase randomized E1B gene-deleted (H101) cisplatin-based chemotherapy treating squamous esophagus].Chin. 2004; 1666-1670PubMed 33Yu Fang Clinical trials China.Curr. Targets. 7: 141-148Crossref (207) JX-594 (Pexavec), Wyeth strain vaccinia disrupted showed hepatocellular carcinoma;34Heo Reid Ruo Breitbach C.J. Rose Bloomston Lim H.Y. Chung H.C. C.W. al.Randomized dose-finding immunotherapeutic liver cancer.Nat. 2013; 19: 329-336Crossref (544) Coxsackievirus A21 (Cavatak), picornavirus (Viralytics, 2016, Society Immunotherapy Cancer, conference). Importantly, perspective, developed clinically non-melanoma indications might never superiority head-to-head comparison depends, extent, how indications. critical question developers must carefully initiating expensive trials. bar progressively higher. Newer drugs always over existing determined higher rates, durability response, survival, lower toxicity, refractory disease. high future indication, race truly show benefit competing platforms However, diverse tropisms naturally occurring viruses, seems highly unlikely could agents histologies. does, however, theoretical edge non-herpes natural behavior HSV-1, precursor reactivate repeatedly throughout life, significant damage face robust adaptive response.35Chentoufi A.A. Benmohamed Mucosal immunopathology ocular genital infections.Clin. Dev. Immunol. 2012: 149135PubMed vaccine neoantigen-reactive pre-existing immunity, like potentially partner therapies. Early data already strongly supportive concept, improved rates III/IV anti-PD1 plus T-VEC.6Puzanov emerging evidence similar synergistic interaction CVA21 conference), unarmed GM-CSF.36Andtbacka Ross M.I. Taylor M.H. Vetto J.T. Neves R.I. Daud Khong H.T. Ungerleider Boran A.D.W. al.Preliminary results II HF10, virus, IIIb, IIIc, 34PubMed Responses observed Detailed lesion receiving complete 46.1% lesions, 30.1% uninjected non-visceral 9.4% visceral lesions.5Andtbacka clear respond they actually get virus. rationale delivery dissemination compelling, expected adequate achieved, maximized. efficient feasible, achieved? barriers intravenous known:1Russell 37Miller NIS reporter virotherapy.Expert 15-32Crossref (49) massive dilution bloodstream; neutralization complement proteins; particle sequestration Kuppfer splenic macrophages; limited permeability neovessels. Considering barriers, easy understand why poor candidate application. manufacture sufficient quantities susceptible rapid circulating anti-HSV-1 50% treatment-eligible patients.38Smith N.J. Age-specific prevalence types 1: global review.J. Infect. Dis. 2002; 186: S3-S28Crossref (683) 39Xu Schillinger J.A. Sternberg M.R. Johnson R.E. Lee F.K. Nahmias Markowitz Seroprevalence coinfection United States, 1988-1994.J. 185: 1019-1024Crossref (214) particles large (150–200 nm) and, hence, less extravasate neovessels, abnormally permeability. Viremic infections typically sustained continuous progeny poliovirus, smallpox) measles-infected monocytes) infection.40Virgin Pathogenesis infection.in: Fields Virology. Volume 1. Lippincott, Williams Wilkins, Philadelphia, PA2007: 327-388Google 41Griffin D.E. Measles virus.in: 2. 1551-1586Google viremia associated, continue appearance antibodies.42Zingher Mortimer Convalescent whole blood, plasma serum prophylaxis measles: JAMA, 12 April, 1926; 1180-1187.Rev. 407-418Crossref (29) 43Moore A.E. destructive Russian Far East transplantable sarcoma 180.Cancer. 1949; 2: 525-534Crossref maximize efficiency d

Language: Английский

---

Fighting Cancer with Mathematics and Viruses

Viruses, Journal Year: 2017, Volume and Issue: 9(9), P. 239 - 239

Published: Aug. 23, 2017

After decades of research, oncolytic virotherapy has recently advanced to clinical application, and currently a multitude novel agents combination treatments are being evaluated for cancer therapy. Oncolytic preferentially replicate in tumor cells, inducing cell lysis complex antitumor effects, such as innate adaptive immune responses the destruction vasculature. With availability different vector platforms potential both genetic engineering regimens enhance particular aspects safety efficacy, identification optimal patient subpopulations or even individual patients becomes top priority. Mathematical modeling can provide support this arena by making use experimental data generate hypotheses about mechanisms underlying biology and, ultimately, predict treatment protocols. Increasingly models be applied account therapeutically relevant parameters components system. In review, we describe current developments mathematical discuss benefit integrating approaches into biological experimentation. Conclusively, propose mutual these research fields increase value preclinical development therapeutic efficacy resulting treatments.

Language: Английский

---

Antibody Inhibition of a Viral Type 1 Interferon Decoy Receptor Cures a Viral Disease by Restoring Interferon Signaling in the Liver

PLoS Pathogens, Journal Year: 2012, Volume and Issue: 8(1), P. e1002475 - e1002475

Published: Jan. 5, 2012

Type 1 interferons (T1-IFNs) play a major role in antiviral defense, but when or how they protect during infections that spread through the lympho-hematogenous route is not known. Orthopoxviruses, including those produce smallpox and mousepox, lympho-hematogenously. They also encode decoy receptor for T1-IFN, T1-IFN binding protein (T1-IFNbp), which essential virulence. We demonstrate T1-IFNs liver locally rather than systemically, T1-IFNbp attaches to uninfected cells surrounding infected foci spleen impair their ability receive signaling, thus facilitating virus spread. Remarkably, this process can be reversed mousepox cured late infection by treating with antibodies block biological function of T1-IFNbp. Thus, our findings provide insights on are evaded viral vivo, unveil novel mechanism antibody-mediated therapy.

Language: Английский

---

Kinetics and Pathogenicity of Equine Herpesvirus-9 Infection following Intraperitoneal Inoculation in Hamsters

Journal of Comparative Pathology, Journal Year: 2011, Volume and Issue: 145(2-3), P. 271 - 281

Published: April 15, 2011

Language: Английский

---

Gene Therapy of Some Genetic Diseases by Transferring Normal Human Genomic DNA into Somatic Cells and Stem Cells from Patients

InTech eBooks, Journal Year: 2011, Volume and Issue: unknown

Published: Nov. 7, 2011

1.1 Viral vectors for gene therapy Gene is a way to correct mutated genes in vivo by transferring normal into cells of patients with genetic diseases or cancers, introduce new express therapeutic proteins. Several viruses like adenoviruses (Nayak & Herzog, 2010; Raper et al., 2003), alphaviruses (Lundstrom, 2001, 2005), retroviruses (Aiuti 2009; Bordignon 1989, 1995; Cavazzana-Calvo 2000; Ferrari 1991; Halatsch 2000), lentiviruses (Dupre 2004; Mortellaro 2006; Nayak 2010), adeno-associated (AAV) (Jayandharan 2011; Terzi Zachariou, 2008), herpes simplex type 1 (HSV-I) (Epstein, 2009), have been used as deliver therapy. However, there were limitations and hurdles using these vectors. Some retroviruses, might integrate human genomic DNA cause cancers (Dave Du 2005; Hacein-Bey-Abina 2003a, 2003b; Z. Li 2002; Modlich Seggewiss 2006). Most can infect both defective/cancer patients, long the receptors (Antar K. Holmes 1997; Norkin, L. Song, Song van den Wollenberg 2008; Houdt this lead serious infections, inflammatory responses, immunological reactions 2010).

Language: Английский

---

Estudo dos herpesvirus humanos tipo 6 e tipo 1 e sua inter-relação com o gene TP53 em diferentes condições patologicas

Published: July 31, 2007

Interacoes entre virus, o sistema imunologico e a acao de enzimas detoxificantes tem sido associadas etiologia muitas doencas incluindo câncer varias auto-imunes. Investigamos papel dos herpes virus tipo 6 (HHV-6) 1 (HHV-1) das variantes do codon 72 (P72) 47 exon 4 TP53, responsaveis por uma diminuicao da atividade antiapoptotica na suscetibilidade ao pele Doenca Basedow-Graves. Utilizamos PCR para deteccao polimorfismos TP53 GSTs, com restricao enzimatica alguns polimorfismos. Quando estudamos 120 pacientes lesoes pele, comparados 41 controles mostramos que infeccao HHV-6 aumenta risco um individuo apresentar carcinoma basocelular (OR=3,182;95%IC:1,125-8,997). O individuos infectados HHV-1 foi aumentado em seis vezes (OR=6,078;95%IC:1,365-27,061). Observamos este tendia ser maior os imunosuprimidos. Estudamos 78 transplantados renais 151 controles. A realmente mais frequente nos (35,89%) (11,25%) (F; p<0,0001). Individuos positivos apareciam frequencia possuiam P72 (60,71%) apresentaram genotipo selvagem Arg/Arg (22%) p=0,001). Para estudarmos relacao as auto-imunes, analisamos 127 diagnostico Basedow-Graves, observando estavam pelo tinham desenvolver esta doenca (OR=2,225;95%IC=1,197-4,135). Pro/Pro estava presente 11,8% Basedow-Graves (p<0,001), aumentando significativamente (OR=28,395; 95%IC=1,658-486,36). Assim, nossos estudos mostram presenca sugerindo esses podem ter malignidades pele; heranca germinativa ha tendencia aumento desenvolvimento quando associamos alelo prolina Ab

---