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Oncolytic viruses:A novel treatment strategy for breast cancer

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Genes & Diseases 2023年第2期10卷 430-446页

作者： Mohammad Javanbakht Sanaz Tahmasebzadeh Luca Cegolon Nasrin Gholami Mandana Kashaki Hassan Nikoueinejad Mohamad Mozafari Mahsa Mozaffari Shi Zhao Mostafa Khafaei Morteza Izadi Saeid Fathi Reza Akhavan-Sigari Nephrology and Urology Research Center Baqiyatallah University of Medical SciencesTehran ***Iran Mehrestan Health Network Iranshahr University of Medical SciencesIranshahr ***Iran University of Trieste Department of MedicalSurgical & Health SciencesTrieste 34128Italy University Health Agency Giuliano-Isontina (ASUGI) Public Health DepartmentTriesteItaly Hematology and Oncology Research Center Tabriz University of Medical SciencesTabriz ***Iran Shahid Akbarabadi Clinical Research Development Unit (ShACRDU) Iran University of Medical Sciences (IUMS)Tehran ***Iran Department of General Surgery Urmia University of Medical ScienceUrmia 57147Iran Department of Pediatrics Iran University of Medical SciencesTehran ***Iran JC School of Public Health and Primary Care Chinese University of Hong KongHong Kong Special Administrative Region 999077China Human Genetics Research Center Baqiyatallah University of Medical SciencesTehran 169875931Iran Health Research Center Baqiyatallah University of Medical SciencesTehran ***Iran Razi Vaccine and Serum Research Institute Agriculture ResearchEducation and Extension Organization (AREEO)Karaj 11365-1558Iran Department of Neurosurgery University Medical CenterTuebingen 72076Germany

Breast cancer,an unceasingly occurring neoplasm,is one of the major determinants of mortality in women.Several ineffective attempts have been pursued using with conventional therapies against breast cancer.Resistance to existing therapies and their respective debilitating adverse effects have led research toward a new era of cancer treatment using viruses.Virotherapy constitutes a developing treatment modality with multiple mechanisms of therapeutic activity in which the viruses can be directly oncolyticand can express transgenes or induce host immune response against tumor cells.Several different DNA-and RNA-containing viruses have been considered for virotherapy of breast cancer including adenovirus,herpes virus,vaccinia,reovirus,Newcastle Disease virus,measles virus and vesicular stomatitis virus.This review aims to summarize the viro-therapeutical agents against breast malignancies.Key Scientific Concepts of Review:In this review paper,we proposed a new strategy to virus's combinatorial treatments using several kinds of transgenes and drugs.These recombinant viruses have provided evidence of treatment efficacy against human breast cancer.

关键词： Adenovirus Breast cancer Herpes virus Measles virus Newcastle disease virus Reovirus vaccinia Vesicular stomatitis virus Virotherapy

SELECTION OF RECOMBINANT vaccinia VIRUSES (TIAN TAN STRAIN) EXPRESSING HEPATITIS B VIRUS SURFACE ANTIGEN BY USING β-GALACTOSIDASE AS A MARKER*

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Science China Chemistry 1990年第2期33卷 188-197页

作者：刘庚起曹旭朱既明任贵方李红梅解燕乡彭薇 Institute of Virology Chinese Academy of Preventive Medicine Beijing 100052 PRC

We constructed a plasmid that contains a small piece of DNA with two vaccinis promoters running in opposite directions——a promoter from a late gene encoding an 11 K polypeptide (P11) and a promoter from an early gene encoding 25K(P25). These promoters were isolated from the Tian Tan strain of vaccinia virus and were flanked by the thymidine kinase (TK) sequence of the same virus. Genes encoding the hepatitis B virus surface antigen (HBsAg) and the Rscherichia coli β-galactosidase (LacZ) were inserted downstream of the 11 K and 25 K promoters respectively so that coexpression plasmids were constructed. Recombinant vaccinis Viruses were selected directly by picking blue plaques formed under overlaying agarose medium containing X-gal. HBsAg was expressed to high level by these recombinant viruses. These recombinant viruses showed reduced virulence on rabbit skin and induced anti-HBs after intrsdermal inoculation of rabbits.

关键词： recombinant vaccinia viruses hepatitis B β-galactosidase

Brazilian vaccinia virus strains show a classical orthopoxvirus infection course and cross-protection

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Asian Pacific Journal of Tropical Medicine 2009年第2期2卷 21-26页

作者： Jaqueline Maria Siqueira Ferreira Betnia Paiva Drumond J?natas Santos Abraho Zélia Inês Portela Lobato Cláudio Ant?nio Bonjardim Paulo César Peregrino Ferreira Erna Geessien Kroon Laboratorio de Virus Departamento de MicrobiologiaInstituto de Ciencias Biologicas Departamento de Medicina Veterinaria Preventiva Escola de VeterindriaUniversidade Federal de Minas Gerais.Avenida Antonio Carlos6627caixa postal 486CEP 31270-901 Belo HorizonteMGBrazil

Objectives:The purpose of this work was to study the infection course and cross-protection in mice after intradermal injection of vaccinia virus(VACV) strain Western Reserve and three Brazilian VACV strains: Aracatuba,Muriae and BeAn58058 isolated from cow,human and rodent,respectively.Methods:Balb/c mice were inoculated by footpad and back scarification and daily monitored regarding lesion development and weight loss.To check cross protection after intradermal VACV inoculation,mice were subsequendy infected with different VACV strains and monitored to check lesion development.Serum neutralization assays were performed to check for the presence of antibodies against Orthopoxvirus.Results:After VACV intradermal inoculation the lesion development pattern was similar in mice infected with the different virus strains.By using the footpad scarification model,cross-protection among VACV strains was observed.Moreover,neutralizing antibodies against Orthopoxvirus were detected in sera from mice infected with all VACV strains.Conclusion:Although it was not possible to observe virulence differences among VACV strains isolated from cow,rodent and human using the murine model,this inoculation route showed to be an appropriated model to study lesions development since it mimics natural infections by VACV in nature.

关键词： Orthopoxvirus Zoonoses Balb/c mice Intradermal injection vaccinia virus Bovine vaccinia outbreaks

Enhancement of DNA vaccine-induced immune responses by a 72-bp element from SV40 enhancer

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Chinese Medical Journal 2007年第6期120卷 496-502页

作者： LI Hai-shan LIU Yong LI Ding-feng ZHANG Ran-ran TANG Hai-li ZHANG Yu-wei HUANG Wei LIU Ying PENG Hong XU Jian-qing HONG Kun-xue SHAO Yi-ming State Key Laboratory for Infectious Disease Prevention and Control National Center for AIDS/STD Control and Prevention Chinese Center for Disease 100050 China

Background Although DNA vaccine is considered as the next generation of vaccine, most DNA vaccine candidates are still suffering from the relatively weak immunogenicity despite the increased dosage of plasmid DNA administered. In order to enhance the immune responses elicited by a codon-optimized HIV gag DNA vaccine, a modified plasmid vector pDRVI1.0 and a booster immunization with replicating Tiantan vaccinia （RTV） strain expressing the same gene were employed. Methods Vector pDRVI1.0 was constructed through inserting the 72-bp element from the SV40 enhancer, which was reported promoting nuclear transport of plasmid DNA, to the upstream of cytomegalovirus enhancer/promoter region of the plasmid vector pVR1012. Gene expression levels from expression plasmids based on pDRVI1.0 and pVR1012 were tested. Humoral and cellular immune responses induced by DNA vaccine alone or DNA prime-RTV boost regimen were determined in mice. Results It was shown that the 72-bp element significantly enhanced the gene expression level in non-dividing cells. gag-specific humoral and cellular immune responses induced by DNA vaccination were both significantly improved, while the Thl/Th2 balance was not obviously affected by the 72-bp element. RTV boosting further significantly enhanced DNA vaccine-palmed antibody and T cell responses in a Thl-biased manner. Conclusions The 72-bp SV40 enhancer element should be included in the DNA vaccine vector and RTV strain is a very efficient live vector for boosting immunization.

关键词： DNA vaccines SV40 enhancer prime-boost vaccinia Tiantan strain

A New Genetically Engineered Vaccine for Animal Growth Promotion

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Science China Chemistry 1994年第10期37卷 1234-1241页

作者：徐文忠杜念兴李光地汪垣李载平 Department of Veterinary Medicine Nanjing Agricultural UniversityNanjing 210095PRC Shanghai Institute of Biochemistry Academia SinicaShanghai 200031PRC

The chemically synthesized somatostatin (ss) gene was fused in phase with the 3′-end ofhepatitis B virus surface antigen (HBsAg) gene.The fusion gene HBs/ss was then recomhined into thegenome of vaccinia virus.This recombinant virus (w-HBs/ss) can express hybrid HBsAg/ss particles whichpresent ss determinants on their surfaces,thereby bearing a good immunogenicity.This new strategical vac-cine of ss can elicit the production of antibody capable of neutralizing ss in the plasma,and consequently en-hance the growth of animals.

关键词： somatostatin genetically-engineered vaccine recombinant vaccinia virus animal growth promotion

EXPRESSION AND SECRETION OF preS CONTAINING HEPATITIS B SURFACE ANTIGEN IN vaccinia VIRUS SYSTEM

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Science China Chemistry 1990年第9期33卷 1070-1077页

作者：汪垣王少芹冯宗铭钟武威孔玉英李载平陆选永姚光弼 Shanghai Institute of Biochemistry Academia Sinica Shanghai 200031 PRC Jing'an Central District Hospital Shanghai PRC

The expression and secretion of preS containing hepatitis B surface antigen in vaccinia virus system was investigated. The human TK^- 143 cells were infected with the recombinant vaccinia viruses vTMS-1 or vTLS-1. Cells infected with vTMS-1, which contains the preS2+S gene, produced preS2 containing middle HBsAg proteins. Similarly, cells produced preS1 containing large HBsAg proteins upon infection with vTLS-1, which carries the preS1+preS2+S gene. The expression products could be secreted and form 22 nm particles. They reacted specifically with anti-preS1 and/or anti-preS2 monoclonal antibodies, and exhibited pHSA-receptor (for polymerized human serum albumin) activity. In addition, the major S components of hepatitis B surface antigen were also present in the products expressed by vTMS-1 and vTLS-1.

关键词： hepatitis B virus vaccinia virus in vivo reeombination HBsAg middle large proteins secretory expression

Construction of a vaccinia virus vectored multi--epitope live vaccine candidate for Plasmodium falciparum

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Journal of Medical Colleges of PLA(China) 1999年第2期14卷 119-123页

作者：董文其李明毕惠祥李英杰

To construct live recombinant vaccinia virus, The HGFSP gene encoding CSP, MSA1, MSA2, RESA,IL-1 and TT epitopes was inserted into the Eec RI and Burn HI sites of pSK plasmid. After digested with Eco RI,bluntly ended by Klenow enzyme and digested with Sac I, the HGFSP gene was cloned into the Sma I and Sac I sites of the vaccinia virus insertion vector (pJ2--16). Recombinant plasmids were identified by gel electrophoresis,restriction enzyme and enzyme map. Results evidenced that HGFSP gene fragment was correctly inserted into the cloning site of hemagglutinin (HA) gene of the pJ2--16 vector. The recombinant plasmids were trans feeted into Cos--7 cells, which were infected with wild type of vaccinia virus Tiantan strain, by means of lipofectamine. Two recombinant vaccinia viruses (HA) were screened and cloned by chicken hemadorption test in BHK21 cells. Indirect immunofluorescence assay (IFA), Dot--ELISA and Western blot with the antibodies against HGFSP protein expressed by E. colt showed that one of the 2 recombinant vaccinia virus expressed desired proteins in infected BHK21 cells. Western blot also showed that the molecular weight of 2 of expressed protein bands was about 23 kDa, according to the theoretical molecular weight of HGFSP protein. Further identification of immunological characters of recombinant virus is under way.

关键词： Plasmodium falciparum vaccinia virus gene vaccine

THE vaccinia VIRUS HindⅢ K FRAGMENT ENCODES A NOVEL PROTEIN BELONGING TO THE SERPIN SUPERFAMILY

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Science China Chemistry 1990年第4期33卷 453-459页

作者：金奇金冬雁侯云德 National Laboratory of Molecular Virology and Virus Genetic Engineering Chinese Academy of Preventive Medicine Beijing 100052 PRC

The 1893-base pair nucleotide sequence of the EcoRⅠ-HindⅢ fragment of vaccinia virus Tiantan strain HindⅢ K clone is determined by the dideoxy chain termination method. A search in the NBRF protein sequence database using FASTA and other microcomputer programs reveals that several proteins belonging to the serpin (serine protease inhibitor) superfamily have striking similarities to tho protein encoded by the HindⅢ Kl ORF. On the basis of the dot-matrix analysis and sequence alignment, the Kl-encoded protein is shown as a novel member of the serpin superfamily. The putative reactive site and switch sequence of this novel serpin are then compared with those of other serpins. The probable evolutionary and possible functional relationships are discussed.

关键词： vaccinia virus serpin superfamily DNA sequencing sequence analysis.

Immune therapy for human papillomaviruses-related cancers

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World Journal of Clinical Oncology 2014年第5期5卷 1002-1019页

作者： Ricardo Rosales Carlos Rosales Virolab S de RL de CV Cuernavaca Morelos 17007 Mexico Carlos Departamento de Inmunología Instituto de Investigaciones Biomédicas Universidad Nacional Autónoma de México Mexico City DF 04510 Mexico

Human papillomaviruses(HPVs) are a large family of double strand DNA viruses comprising more than 180 types. Infection with HPV is very common and it is associated with benign and malignant proliferation of skin and squamous mucosae. Many HPVs, considered lowrisk such as HPV 6 and 11, produce warts; while highrisk viruses, such as HPVs 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, and 58, induce tumors. About 5% of all cancers in men and women are associated with HPV infection. Because there are not antiviral drugs for HPV infection, current therapies for low-risk HPV infections involve physical removal of the lesion by cryotherapy, trichloracetic acid, laser, or surgical removal. Surgical procedures are effective in the treatment of precancerous lesions, however after these procedures, many recurrences appear due to new re-infections, or to failure of the procedure to eliminate the HPV. In addition, HPV can inhibit recognition of malignant cellsby the immune system, leading to the development of cancer lesions. When this occurs, radiotherapy and chemotherapy are then used. Unfortunately, about 50% of the HPV-cancer patients still die. In the past decade, a better knowledge of the natural history of the virushost interaction and of the immune response against this viral infection has brought new therapeutic strategies geared to modulate the immune system to generate an efficient virus-specific cytotoxic response. Novel HPV protein-expressing vaccines have shown some significant clinical efficacy and systemic HPV-specific cytotoxic T cell responses. This review will describe the current status of the several therapeutic strategies used to treat HPV-induced lesions, and discuss the various new therapies now being tested.

关键词： Human papillomavirus T cell Immunoglobulin Antibody vaccinia virus