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ABSTRACT 'Naked' nucleic acid vaccines are potentially useful candidates for the treatment of patients with cancer1,2,3, but their clinical efficacy has yet to be demonstrated. We

sought to enhance the immunogenicity of a nucleic acid vaccine by making it 'self-replicating'. We accomplished this by using a gene encoding an RNA replicase polyprotein derived

from the Semliki forest virus, in combination with a model antigen. A single intramuscular injection of a self-replicating RNA immunogen elicited antigen-specific antibody and CD8+ T-cell

responses at doses as low as 0.1 μg. Pre-immunization with a self-replicating RNA vector protected mice from tumor challenge, and therapeutic immunization prolonged the survival of mice with

established tumors. The self-replicating RNA vectors did not mediate the production of substantially more model antigen than a conventional DNA vaccine did _in vitro_. However, the enhanced

efficacy _in vivo_ correlated with a caspase-dependent apoptotic death in transfected cells. This death facilitated the uptake of apoptotic cells by dendritic cells, providing a potential

mechanism for enhanced immunogenicity. Naked, non-infectious, self-replicating RNA may be an excellent candidate for the development of new cancer vaccines. Access through your institution

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OTHERS CLINICAL TRIALS OF SELF-REPLICATING RNA-BASED CANCER VACCINES Article Open access 10 February 2023 SELF-REPLICATING VEHICLES BASED ON NEGATIVE STRAND RNA VIRUSES Article 15 February

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al._ Real-time quantitative RT-PCR after laser-assisted cell picking. _Nature Med._ 4, 1329–1333 (1998). Article  CAS  Google Scholar  Download references ACKNOWLEDGEMENTS The authors thank

S.A. Rosenberg for reading the manuscript and for discussions, A. Atwood for help with vector construction, T. Dubensky (Chiron) for advice, M. Blalock for graphics, P. Spiess for help with

animal experiments, and S. Wolf (Genetics Institute) for his gift of rmIL-12. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Surgery Branch, National Cancer Institute, Building 10, Room 2B42,

10 Center Drive, Bethesda, 20892-1502, Maryland, USA Han Ying, Tal Z. Zaks, Rong-Fu Wang, Kari R. Irvine, Udai S. Kammula, Francesco M. Marincola, Wolfgang W. Leitner & Nicholas P.

Restifo Authors * Han Ying View author publications You can also search for this author inPubMed Google Scholar * Tal Z. Zaks View author publications You can also search for this author

inPubMed Google Scholar * Rong-Fu Wang View author publications You can also search for this author inPubMed Google Scholar * Kari R. Irvine View author publications You can also search for

this author inPubMed Google Scholar * Udai S. Kammula View author publications You can also search for this author inPubMed Google Scholar * Francesco M. Marincola View author publications

You can also search for this author inPubMed Google Scholar * Wolfgang W. Leitner View author publications You can also search for this author inPubMed Google Scholar * Nicholas P. Restifo

View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Nicholas P. Restifo. RIGHTS AND PERMISSIONS Reprints and

permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Ying, H., Zaks, T., Wang, RF. _et al._ Cancer therapy using a self-replicating RNA vaccine. _Nat Med_ 5, 823–827 (1999).

https://doi.org/10.1038/10548 Download citation * Received: 28 April 1999 * Accepted: 19 May 1999 * Issue Date: July 1999 * DOI: https://doi.org/10.1038/10548 SHARE THIS ARTICLE Anyone you

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