Tumour cell expression of B7 costimulatory molecules and interleukin-12 or granulocyte–macrophage colony-stimulating factor induces a local antitumour response and may generate systemic protective immunity

Chong, Heung; Todryk, Stephen; Hutchinson, Gill; Hart, I. R.; Vile, R. G.

doi:10.1038/sj.gt.3300584

Cited by 59 publications

(37 citation statements)

References 48 publications

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“…The first, pBabe-GALV, is an Mo-MLV-derived C-type retroviral vector, of the type that we have previously used for the high efficiency of transfer of therapeutic genes to tumour cells. 19,20 In this vector, the GALV FMG cDNA is expressed from the Mo-MLV LTR in infected cells. The second, Lenti-GALV, was constructed from an HIV-based self inactivating vector in which the 3ЈLTR is transcriptionally disabled.…”

Section: Retroviral Vectors Expressing the Galv Fmgmentioning

confidence: 99%

A lentiviral vector expressing a fusogenic glycoprotein for cancer gene therapy

et al. 2000

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The gibbon ape leukaemia virus envelope fusogenic membrane glycoprotein (GALV FMG) is a highly potent cytotoxic gene with great potential for use in cancer gene therapy. Here, we show that production of a VSV-G pseudotyped lentiviral vector expressing GALV FMG reconciles the requirements of viral production with the cytotoxic effects of GALV in human cells and has high titres on both dividing and quiescent tumour cells. Direct intratumoral injection of these stocks eradicated progressively growing human tumour xen-

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Section: Retroviral Vectors Expressing the Galv Fmgmentioning

confidence: 99%

A lentiviral vector expressing a fusogenic glycoprotein for cancer gene therapy

et al. 2000

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“…GM-CSF and CD80 have definite function and have been widely used in cancer gene therapy. [37][38][39] Their therapeutic effect has been widely recognized, so we chose them as transgenes for our CRAD. The expression of GM-CSF and CD80 was greatly improved in tumor cells infected by Ad-CD80-TPE-GM, compared with cells infected by the control Ad (Figures 2b and c).…”

Section: Discussionmentioning

confidence: 99%

A simplified system for generating oncolytic adenovirus vector carrying one or two transgenes

Zb¹,

Wu²,

Wang³

et al. 2007

Cancer Gene Ther

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Oncolytic adenoviruses, also called conditionally replicating adenoviruses (CRADs), have been widely applied in cancer gene therapy. However, the construction of CRADs is still time-consuming. In this study, we attempted to establish a simplified method of generating CRADs based on AdEasy system. A novel plasmid pTE-TPE-GM was constructed, containing sequentially positioned promoter of telomerase reverse transcriptase (TERTp), coding sequence of E1A gene, promoter of E1B gene, granulocytemacrophage colony-stimulating factor (GM-CSF) gene, internal ribosome entry site sequence and coding sequence of E1B55K gene. The CRAD-generating system reported here include three plasmids: pTE-TPE-GM, pShuttle-CMV and AdEasy-1, one Escherichia coli strain BJ5183, and the packaging cell line 293. Using this system, an oncolytic adenovirus carrying B7-1 (CD80) and GM-CSF genes was successfully constructed and designated as Ad-CD80-TPE-GM. The expression of GM-CSF increased more than 9000 times in tumor cell lines infected by Ad-CD80-TPE-GM at a multiplicity of infection (MOI) of 5, compared with the cells infected by replication-defective control virus. Similarly, the expression of CD80 also increased 9-140 times. Ad-CD80-TPE-GM selectively replicates in TERT-positive tumor cells, and the progeny viruses can reach up to 375 infection units (IU) per cell. In vitro study showed that the Ad-CD80-TPE-GM induced an obvious oncolytic effect at MOI of 0.1, and killed about 80% TERT-positive tumor cells within 7 days at an MOI of 1. The antitumor effect of this vector was also investigated in Hep2 xenograft model of nude mice, and the tumor inhibition rate reached 74% at day 30 after the administration with a total dose of 1 Â 10 9 IU Ad-CD80-TPE-GM. Intratumoral injection of Ad-CD80-TPE-GM slightly induced neutralizing antibody against the oncolytic adenovirus in nude mice, which might contribute to the virus clearance in vivo. In conclusion, we successfully constructed an oncolytic CRAD carrying GM-CSF and CD80 gene. More importantly, this system can be modified to generate novel transcriptionally regulated CRADs with different tissue-specific promoters or transgenes.

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“…To our mind, they are unfortunately also based on a combination of cytokines and receptors from the second part of the table; in other words, on mediators of adaptive immunity, [64][65][66][67] excluding rare exceptions, which combine molecules of both arms of immune response. 68 In most cases involving genetic modification, amplification of immune response induced by a combination of immunoregulatory molecules was usually reported.…”

Section: Immune System Mediators In Gene Therapy Of Cancermentioning

confidence: 99%

“…Thus, a combination of these cytokines is a powerful tool, as it was reported. 65 The main cause of such amplifications of the immune GM-CSF Mouse models and clinical trial of autologous irradiated tumor cells generated by ex vivo transfection [23,63] Gene transfer approaches in cancer immunotherapy SS Larin et al system response is the involvement of different and independent mechanisms of adoptive immune response.…”

Section: Immune System Mediators In Gene Therapy Of Cancermentioning

confidence: 99%