Kenneth Lundstrom PhD Contents

The Revised Authoritative Guide To Vaccine Legal Exemptions

Vaccines Have Serious Side Effects

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Introduction

Alphavirus Used in Cancer Vaccines

Alphavirus for the Transfection of Tumor Cell Lines

Intratumoral Gene Delivery by Alphavirus

Tumor Targeting of Alphavirus Vectors

Production of Retrovirus-Like Particles by Alphavirus

Safety of Alphavirus Vectors

Vector Development

Conclusions and Future Prospects

Summary

Alphavirus vectors can infect a broad range of mammalian cells both in cell cultures and in vivo. The presence of the RNA replicon generates extreme RNA levels in infected cells, which is the basis for the very high levels of heterologous gene expression. Application of replication-deficient vectors leads to short-term expression, which makes these vectors highly attractive for cancer gene therapy. Alphaviruses can be used as vaccine vectors for both prophylactic and therapeutic applications. In this context, the P185 tumor antigen and human papilloma virus gene E7, when administered in mice, resulted in protection against tumor challenge and tumor regression in animals with pre-existing tumors. Alphavirus vectors carrying therapeutic or toxic genes used for intratumoral injections have demonstrated efficient tumor regression. For systemic delivery, expression targeting has been obtained by the introduction of targeting sequences in the envelope structure of the virus. Alternatively, alphavirus particles have been encapsulated in liposome, which can target tumor cells.

Key Words: Alphavirus vectors; cancer vaccines; intratumoral injection; tumor targeting.

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