Semliki Forest virus-based vaccines: persistence, distribution and pathological analysis in two animal systems

Morris-Downes, M.; Phenix, K. V.; Smyth, Joan A.; Sheahan, B. J.; Lileqvist, Sissela; Mooney, Dorothy A.; Liljeström, Peter; Todd, D.; Atkins, Gregory J.

doi:10.1016/s0264-410x(00)00428-x

Cited by 56 publications

(34 citation statements)

References 40 publications

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“…9 The SFV vector system has several advantages over other vector systems in its broad host range and inherent ability to induce apoptosis. 10 SFV vectors have been successfully used to induce in vivo expression of a number of genes such as cytokines, [11][12][13] tumour-associated antigens (TAA), 13,14 and vaccine antigens, 15,16 and to deliver therapeutic genes to the central nervous system. 17 It has been shown that recombinant SFV (rSFV) particles can efficiently infect tumour cells and that intratumoural treatment with rSFV particles results in the induction of p53-independent apoptosis leading to significant tumour inhibition.…”

Section: Introductionmentioning

confidence: 99%

Regression of mouse tumours and inhibition of metastases following administration of a Semliki Forest virus vector with enhanced expression of IL-12

et al. 2005

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The Semliki Forest virus (SFV) vector is an RNA-based suicide expression vector that has been used experimentally for tumour therapy. Recently, a new enhanced vector pSFV10-E has been developed that expresses foreign genes at levels up to 10 times higher than the original vector. Interleukin-12 (IL-12), an immunomodulatory cytokine, plays a key role in the induction of T-helper1 responses. The two IL-12 gene subunits were cloned from mouse splenocytes and inserted into the pSFV10-E and pSFV10 (nonenhanced) vectors. Both constructs expressed and secreted biologically active murine IL-12. Administration of high titre rSFV10-E-IL12 particles intratumourally to treat implanted K-BALB tumours in BALB/c mice demonstrated complete tumour regression in comparison to control or rSFV10-IL12 treated groups. High titre rSFV10-E-IL12 particles were also effective in the CT26 tumour model. Histological and immunohistochemical studies revealed tumour necrosis in addition to aggressive influx of CD4+ and CD8+ T cells and other immune cells. Furthermore, inhibition of primary tumour growth and lung metastases of a metastatic (4T1) tumour model indicated the potential of high titres of rSFV10-E-IL12 particles as an efficient antitumour therapeutic agent.

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Section: Introductionmentioning

confidence: 99%

Regression of mouse tumours and inhibition of metastases following administration of a Semliki Forest virus vector with enhanced expression of IL-12

et al. 2005

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“…44 In contrast to SFV particles, injected nucleic acids are distributed more easily through the body of experimental animals and persist much longer. 45 However, their persistence is a contraindication for expression of the apoptosis-inducing RNA replicase. A comparison of the efficacy of recombinant SFV particle immunization with DNA or RNA immunization encoding the same antigen showed that SFV particles induce stronger immune responses.…”

Section: Discussionmentioning

confidence: 99%

“…A comparison of the efficacy of recombinant SFV particle immunization with DNA or RNA immunization encoding the same antigen showed that SFV particles induce stronger immune responses. 45 Here, we set out to investigate the potential of the recombinant SFV system for the production of GM-CSFsecreting, autologous tumor cell vaccines. These vaccines can be used, for instance, as adjuvant therapies for the treatment of patients at high risk of metastases after the primary tumor is surgically removed.…”

Section: Discussionmentioning

confidence: 99%

Replication-defective recombinant Semliki Forest virus encoding GM-CSF as a vector system for rapid and facile generation of autologous human tumor cell vaccines

et al. 2001

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“…16 In the vast majority of published studies (Table 1), there was no spiked material. Some authors also used an internal control, which is often a competitive piece of DNA used in the same reaction tube.…”

Section: Technique Validationmentioning

confidence: 99%

Gene transfer vector biodistribution: pivotal safety studies in clinical gene therapy development

Gonin

Gaillard

2004

Gene Ther

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Techniques allowing for gene transfer vectors biodistribution investigation, in the frame of preclinical gene therapy development, are exposed. Emphasis is given on validation and test performance assessment. In the second part, specific gene vector distribution properties are reviewed (adenovirus, AAV, plasmid, retroviruses, herpes-derived vectors, germline transmission risks). The rationale for biodistribution by quantitative PCR, animal study and result interpretation is discussed. The importance and pivotal role of biodistribution study in gene transfer medicine development is shown through the determination of target organs for toxicity, germline transmission assessment and determination of risks of shedding and spreading of vectors in the gene transfer recipient and the environment.

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Semliki Forest virus-based vaccines: persistence, distribution and pathological analysis in two animal systems

Cited by 56 publications

References 40 publications

Regression of mouse tumours and inhibition of metastases following administration of a Semliki Forest virus vector with enhanced expression of IL-12

Regression of mouse tumours and inhibition of metastases following administration of a Semliki Forest virus vector with enhanced expression of IL-12

Replication-defective recombinant Semliki Forest virus encoding GM-CSF as a vector system for rapid and facile generation of autologous human tumor cell vaccines

Gene transfer vector biodistribution: pivotal safety studies in clinical gene therapy development

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