For a long time past viruses have been recognized as being tumoricidal. At present, researchers are still pursuing studies and constructing more suitable oncolytic viruses for treating different malignant tumors. Herpes simplex virus type 1 (HSV-1) has been known as the most potential oncolytic virus among all the viruses. In this overview, we summarize the current situation of oncolytic viruses, the biology of HSV-1, its construction and application of its recombinant, and we debate on the feasibility and prospect of HSV-1 mutants labeled with radionuclides for cancer therapy.
Herpesvirus 1, Human ; genetics ; physiology ; Humans ; Mutation ; Neoplasms ; radiotherapy ; Oncolytic Virotherapy ; methods ; trends ; Oncolytic Viruses ; genetics

Naturally existing Newcastle disease virus (NDV) can specifically execute oncolytic ability in clinical studies. Reports from clinical trials using NDV as oncolytic agents showed promise and warrant results in cancer therapy. In recent years, reverse genetics technology has been used widely in the studies of NDV virology. More recently, the technology was applied to optimize the oncolytic efficacy of NDV, for instance, modification of the F gene, and expression of GM-CSF, IFN-gamma, IL-2 or TNF-alpha. NDV is widely investigated in cancer therapy and will definitely offer a prosperous future for clinical cancer therapeutics. We reviewed the developments of cancer therapy by recombinant NDV using reverse genetics technology, as well as our own experience in this domain.
Animals ; Humans ; Neoplasms ; pathology ; therapy ; Newcastle disease virus ; genetics ; physiology ; Oncolytic Virotherapy ; methods ; Oncolytic Viruses ; genetics ; physiology ; Recombination, Genetic

Oncolytic adenoviruses (Ads), which are live, replication-competent viruses that can selectively replicate in tumor cells and lead to cell lysis, have been used in tumor therapy. But due to the complexity and high mutability of human tumors, it becomes a major strategy to improve the selectivity, efficacy, and safety of oncolytic Ads. The oncolytic Ads that can express short hairpin RNA, cytokines, suicide gene, and matrix-modulating proteins have higher antitumor activity than the wild type. Tumor-specific promoters, especially hTERT and HRE promoters, increase the selectivity of oncolytic Ads for tumor cells. Moreover, oncolytic Ads surface-modified by polyethylene glycol (PEG), liposomes, biodegradable nanoparticles, and polypeptides have reduced immunogenicity and hepatotoxicity and improved antitumor activity when systemically administered, and the selectivity of oncolytic Ads can be significantly increased when linking PEG to antibodies, small peptides, cytokines, and ligands. Therefore, engineered oncolytic Ads combining the advantages of viral and non-viral vectors, as well as immunotherapy, are a promising strategy for improving the efficacy of targeted virotherapy.
Adenoviridae ; genetics ; physiology ; Animals ; Humans ; Neoplasms ; therapy ; virology ; Oncolytic Virotherapy ; trends ; Virus Replication

Oncolytic virotherapy is a novel cancer therapy. Vaccine-attenuated strains of measles virus(MV)is an ideal candidate for oncolytic virotherapy which has an excellent safety record. Vaccine-attenuated MV uses CD46 and Nectin-4 molecule as major entry receptors into cells. Vaccine-attenuated MV can selectively infect and kill a wide variety of cancer cells in vitro and in vivo. With the development of molecular cloning, scientists have successfully rescued cDNA of vaccine-attenuated MV and increased its oncolytic efficiency with molecular engineering techniques. Phase I clinical trials of virotherapy for ovarian cancer and multiple myeloma with vaccine-attenuated MV are underway. The preliminary results indicate the promising antitumor potential of vaccine-attenuated MV.
Clinical Trials, Phase I as Topic ; Humans ; Measles virus ; Neoplasms ; therapy ; Oncolytic Virotherapy

OBJECTIVE: To study the result of HNE-1 cancer cells lesion and HNE-1 cancer cells apoptosis caused by vesicular stomatitis virus in vitro. METHOD: Firstly, HNE-1 cancer cells of human nasopharyngeal carcinoma were cultured in vitro. Secondly, tumor cells were treated with vesicular stomatitis virus (VSV) in different concentration (0.1 moi, 1.0 moi, 10.0 moi and 100.0 moi), while cells without treatment were used as blank assay. Finally, we observed the lesion of HNE-1 cells treated with VSV for 24 to 48 hours under invert microscope, compared with HNE-1 cells of blank assay. By measurement of MTT reduction assay and Hoechst 33258- staining under fluorescence microscope, the effect of VSV killing HNE-1 cancer cells and the induction of apoptosis by VSV in HNE-1 cancer cells were investigated in vitro. RESULT: Compared with blank assay, HNE-1 cancer cells of human nasopharyngeal carcinoma treated with VSV showed phenomenon of lesion under invert microscope. Followed the increase of concentration of VSV, cell survival rate of HNE-1 cancer cells decreased. The research methods of MTT reduction assay and Hoechst 33258 staining under fluorescence microscope defined the effect of VSV killing HNE-1 cancer cells and confirmed that VSV inducing apoptosis of HNE-1 cancer cells in vitro. CONCLUSION VSV not only exhibited the anti-tumor activity in HNE-1 cancer cells of human nasopharyngeal carcinoma but also showed the potential power of inducing apoptosis of HNE-1 cancer cells in vitro.
Apoptosis ; Cell Line, Tumor ; Cell Survival ; Humans ; Nasopharyngeal Neoplasms ; pathology ; Oncolytic Virotherapy ; Vesiculovirus

Human adenoviruses are widespread causative agent that induces respiratory diseases, epidemic keratoconjunctivitis and other related diseases. Adenoviruses are commonly used in experimental and clinical areas. It is one of the most commonly used virus vectors in gene therapy, and it has attracted a lot of attention and has a high research potential in tumor gene therapy and virus oncolytic. Here, we summarize the biological characteristics, epidemiology and current application of adenovirus, in order to provide reference for engineering application of adenovirus.
Adenovirus Infections, Human ; epidemiology ; virology ; Adenoviruses, Human ; genetics ; Genetic Engineering ; methods ; trends ; Genetic Vectors ; Humans ; Oncolytic Virotherapy ; trends ; Oncolytic Viruses ; genetics ; Virus Replication

OBJECTIVETo construct an oncolytic adenovirus with the DD3 promoter regulation, expressing small hairpin RNA and targeting the SATB1 gene (SATBI-shRNA), and to evaluate its potential for inhibiting the growth of human prostatic carcinoma cells (LNCaP) in vitro.

METHODSSATB1-shRNA expression cassettes containing the H1 promoter were produced by PCR from pSilencer3. 1-SATB1 and inserted into the pZD55 vector, and the recombinant plasmid pZD55-SATB1-shRNA was constructed, pZD55SATB1-shRNA and pZXC2-DD3-E1A were digested with EcoRV and Xba I , and the obtained expression cassettes linked each other to construct the recombinant plasmid pDD3-ZD55-SATB1, which was cotransfected with the pBHGE3 packaging plasmids mixture into 293 cells by Effectence. The recombined adenoviruses DD3-ZD55-SATB1 were identified by PCR. Viruses were propagated on HEK293 cells and purified by standard techniques, and the functional PFU titers determined by plaque assay on 293 cells. The antitumor potential of DD3-ZD55-SATB1 to LNCaP was evaluated by the crystal violet dye method. The expression level of the E1A gene was detected by Western blot, and that of the SATB1 gene in the adenovirus-infected LNCaP cells by both Western blot and RT-PCR.

RESULTSAn oncolytic adenovirus expressing SATB1-shRNA with the DD3 promoter regulation, DD3-ZD55-SATB1, was constructed successfully, whose functional PFU titer was 1.2 x 10(10) PFU/ml. DD3-ZD55-SATB1 showed an obvious cytopathic effect and a selective expression of E1A in the adenovirus-infected LNCaP cells; it exhibited a high LNCaP-targetability and specific SATB1-silencing effect.

CONCLUSIONThe successful construction of the oncolytic adenovirus DD3-ZD55-SATB1 offers a new tool for researches on the gene therapy for human prostate cancer.

Adenoviridae ; genetics ; Carcinoma ; therapy ; Cell Line, Tumor ; Genetic Vectors ; Humans ; Male ; Matrix Attachment Region Binding Proteins ; genetics ; Oncolytic Virotherapy ; methods ; Oncolytic Viruses ; genetics ; Promoter Regions, Genetic ; Prostatic Neoplasms ; therapy ; RNA Interference ; RNA, Small Interfering ; genetics

In order to evaluate the biological activity in vitro and the antitumor effects of 131I-conditionally replicating oncolytic adenovirus KH901 on HepG2 human hepatoma xenografts, the leves of GM-CSF expression were determined by ELISA method. A panel of tumor and normal cells was infected with recombinant adenovirus KH901 at MOI of 10 PPC. The medium was harvested to determine the bioactivity of GM-CSF after 24 hours. Nude mice bearing HepG2 human hepatoma xenografts were given 131-KH901. Antitumor effects were assessed using endpoints of tumor growth delay. The data showed that after 24 hours 131-KH901 replicated hugely in tumor cells and produced significant amount of GM-CSF 183.27 +/- 6.90 pg/ml, while producing very small amount of GM-CSF 20.44 +/- 0.77 pg/ml in normal cells. In the treatment of tumor, 131I-KH901 showed higher restraint rate (71.3%) compared to 131I (22.7%) or KH901 (52.7%). Therefore, 131-KH901 can inhibit the growth of human hepatoma cell in nude mice and it may be a potential drug for treating liver cancer.
Adenoviridae ; genetics ; metabolism ; Animals ; Female ; Granulocyte-Macrophage Colony-Stimulating Factor ; genetics ; metabolism ; Hep G2 Cells ; Humans ; Iodine Radioisotopes ; Liver Neoplasms, Experimental ; diagnostic imaging ; pathology ; virology ; Male ; Mice ; Mice, Nude ; Oncolytic Virotherapy ; Oncolytic Viruses ; genetics ; metabolism ; Radionuclide Imaging

The E1A gene was obtained by PCR with QBI-293A cell genome DNA as template. After enzyme digestion, the E1A gene was ligated to transfer vector pAdTrack-CMV. The positive clone pAdTrack-CMV-E1A were lineared by PmeI and co-transformed with pAdEasy-1 in BJ5183 E. coli. The recombinant adenovirus vector pAdEasy-1-pAdTrack-CMV-E1A were digested by PacI and transfected into QBI-293A cells with liposomes. The oncolytic recombinant adenovirus Ad-E1A was obtained after 7 days. The results showed that this oncolytic adenovirus Ad-E1A can replicate in ECV304 cells and inhibit growth of ECV304 cell. In addition, it also decreased the secretion of VEGF and expression of NF-kappaB of ECV304 cells, indicating that Ad-E1A have potential of inhibition of tumor metastasis.
Adenoviridae ; genetics ; physiology ; Adenovirus E1A Proteins ; biosynthesis ; genetics ; Cell Proliferation ; Cells, Cultured ; Endothelial Cells ; cytology ; metabolism ; Humans ; Oncolytic Virotherapy ; Oncolytic Viruses ; genetics ; physiology ; Promoter Regions, Genetic ; Umbilical Veins ; cytology ; metabolism

Oncolytic herpes simplex virus (HSV) can replicate in and kill cancer cells without harming normal tissue. G47delta is a third-generation HSV vector. In this study, the therapeutic effects of G47delta on human nasopharyngeal carcinoma (NPC) were determined in vitro and in vivo. The human NPC cell lines CNE-2 and SUNE-1, primary normal nasopharyngeal epithelial cells (NPECs), and immortalized nasopharyngeal cells NP-69 and NPEC2/Bmi1 were infected with G47delta at different multiplicities of infection (MOIs). The survival of infected cells was observed daily. Two subcutaneous models of NPC were established with CNE-2 and SUNE-1 in Balb/c nude mice. G47delta or virus buffer as control was injected into the subcutaneous tumors. Tumor size was measured twice a week, and animals were euthanized when the diameter of their tumors exceeded 18 mm or when the animals appeared moribund. For the NPC cell lines CNE-2 and SUNE-1, more than 85% and 95% of cells were killed on day 5 after G47delta infection at MOI = 0.01 and MOI = 0.1, respectively. Similar results were observed for an immortalized cell line NPEC2/Bmi-1. A moderate effect of G47delta was also found on another immortalized cell line NP-69, of which only 27.7% and 75.9% of cells were killed at MOI = 0.01 and MOI = 0.1, respectively. On the contrary, there was almost no effect observed on NPECs. The in vivo experiments showed that tumors in mice in the G47delta-treated group regressed completely, and the mice exhibited much longer survival time than those in the control groups. Our results suggest that the potential therapeutic effects of G47delta would be applicable for treatment of NPC patients in the future.
Animals ; Apoptosis ; Carcinoma ; Cell Line, Tumor ; Female ; Humans ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Nasopharyngeal Neoplasms ; pathology ; therapy ; virology ; Oncolytic Virotherapy ; methods ; Oncolytic Viruses ; physiology ; Simplexvirus ; physiology ; Xenograft Model Antitumor Assays