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

Withoff, Sebo; Glazenburg, KL; Veen, ML van; Kraak, M; Hospers, Geke A.P.; Störkel, Stephan; Vries, Elisabeth G.E. de; Wischut, J; Daemen, Toos

doi:10.1038/sj.gt.3301556

Cited by 3 publications

(3 citation statements)

References 46 publications

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“…The antitumoural effect could possibly be further enhanced by the introduction of cytotoxic or antiangiogenic factors (including cytokines) into the vector, which would be secreted by cells and diffuse through the tumour. [14][15][16][17][18][19]36 In this study, we have administered VLPs expressing a viral antigen. This could induce a neutralizing immune response that may affect subsequent administrations.…”

Section: Treatment Of K-balb and Ct26 Tumours With Sfv Jwp Smyth Et Almentioning

confidence: 99%

“…[15][16][17][18] Phase I and II clinical trials are currently planned to use liposome-encapsulated SFV vectors in the treatment of several tumours, including glioblastoma multiforme. 19 The use of replication proficient oncolytic viruses is now re-emerging as a possibility for tumour therapy, and viruses have been described that grow preferentially in tumour cells.…”

Section: Introductionmentioning

confidence: 99%

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Treatment of rapidly growing K-BALB and CT26 mouse tumours using Semliki Forest virus and its derived vector

et al. 2004

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Section: Treatment Of K-balb and Ct26 Tumours With Sfv Jwp Smyth Et Almentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Treatment of rapidly growing K-BALB and CT26 mouse tumours using Semliki Forest virus and its derived vector

et al. 2004

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“…Thus, upon rVEE injection, DCs might become infected at the site of injection and subsequently migrate to local lymph nodes where they can evoke an immune response. SFV, on the other hand, transfects a variety of cells such as fibroblasts, primary human tumour cells, murine tumour cells lines [25,26], cardiovascular cells and smooth muscle cells [27] but, as mentioned above, not DCs. The immune response evoked by SFV immunization occurs via cross-priming of antigen by DCs that have taken up apoptotic rSFV transfected cells [9].…”

Section: A B C Dmentioning

confidence: 99%

Superior Therapeutic Efficacy of Alphavirus-Mediated Immunization against Human Papilloma Virus Type 16 Antigens in a Murine Tumour Model: Effects of the Route of Immunization

et al. 2004

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In our efforts to develop a strong, effective immune response against cervical carcinoma and premalignant disease, we study the use of recombinant Semliki Forest virus (SFV) encoding the oncoproteins E6 and E7 from high-risk human papilloma viruses (HPVs). Optimal immunization conditions are required for immunotherapeutic treatment of cervical cancer as it has been postulated that cervical cancer patients are immune-suppressed and/or immunologically tolerant for HPV. We previously generated an optimized construct encoding a fusion protein of HPV16 E6 and E7 and a translational enhancer (enhE6,7). Immunization of mice with SFV-enhE6,7 was shown to induce cytoxic T cell (CTL) responses and resulted in the eradication of established tumours. We now demonstrate, using HPV16-specific MHC class I tetramers, that high pCTL frequencies can be induced. However, this induction is strongly influenced by the route of immunization applied. Whilst in bulk CTL assays, requiring in vitro restimulation, CTL activity can be observed upon sc, ip, iv and im immunization, detectable pCTL frequencies, without in vitro restimulation, are only induced upon im and iv immunization. The route of immunization also strongly influences the dose of viral vector needed to induce CTLs and tumour therapy. As few as 5x104 SFV-enhE6,7, primed and boosted iv, are needed to eradicate tumours in six out of seven mice treated. Furthermore, exponentially growing tumours of approximately 500 mm3 in size were seen to completely resolve and even tumours as large as 1500 mm3 decreased to one-third of their size. Apart from this potency, SFV vectors can safely be used for the expression of oncoproteins such as E6 and E7, since the viral RNA is not integrated in the host genome. Thus SFV-enhE6,7 meets with the criteria that a vaccine against cervical cancer should be safe and induce a very strong, long-lasting CTL response, strong enough to eradicate existing tumours.

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Alphaviral-Based Strategies for the Immunotherapy of Cancer

Nelson¹,

Smith²

2004

Handbook of Cancer Vaccines

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

Abstract: This paper describes the production of recombinant Semliki

Cited by 3 publications

References 46 publications

Treatment of rapidly growing K-BALB and CT26 mouse tumours using Semliki Forest virus and its derived vector

Treatment of rapidly growing K-BALB and CT26 mouse tumours using Semliki Forest virus and its derived vector

Superior Therapeutic Efficacy of Alphavirus-Mediated Immunization against Human Papilloma Virus Type 16 Antigens in a Murine Tumour Model: Effects of the Route of Immunization

Alphaviral-Based Strategies for the Immunotherapy of Cancer

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