Evidence map›Paper›PMID 10395329›Full record

ArticleNature medicine1999

Cancer therapy using a self-replicating RNA vaccine.

H Ying, T Z Zaks, R F Wang, K R Irvine, U S Kammula, F M Marincola, W W Leitner, N P Restifo

Open access · greenAbstract read
In one paragraph

Article in Nature medicine, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers.

0numbers the graph read from it
0cells of the map it votes in
107citing papers in PubMed
8.7field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

107 citing papers in PubMed, 323 citations in OpenAlex.

  1. Trial
  2. Article
  3. Immunology of RNA-based vaccines: The critical interplay between inflammation and expression.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
  4. Messenger RNA vaccines in the prevention of allergic diseases.The World Allergy Organization journal · 2025
    Review
  5. Research progress of mosquito-borne virus mRNA vaccines.Molecular therapy. Methods & clinical development · 2025
    Review
  6. Viral Vector-Based Cancer Vaccines.Methods in molecular biology (Clifton, N.J.) · 2025
    Article
  7. Review
  8. Cancer biotherapy: review and prospect.Clinical and experimental medicine · 2024
    Review
  9. Article
  10. Review
  11. Article
  12. Review
  13. Review
  14. Review
  15. Review
  16. Review
  17. Review
  18. The Delivery of mRNA Vaccines for Therapeutics.Life (Basel, Switzerland) · 2022
    Review
  19. Multimeric RNAs for efficient RNA-based therapeutics and vaccines.Journal of controlled release : official journal of the Controlled Release Society · 2022
    Review
  20. Review

47 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 1 institution in 1 country.

H YingSurgery Branch, National Cancer Institute, Bethesda, Maryland 20892-1502, USA.
T Z Zaks
R F Wang
K R Irvine
U S Kammula
F M Marincola
W W Leitner
N P Restifo
National Cancer Institute · US

Funding

Building on the success of the adoptive immunotherapy of cancerZ01BC010763 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI RESTIFO, NICHOLAS P · 2006 to 2008
$6.4M
Intramural NIH HHS Z01 BC010763Intramural NIH HHS Z99 CA999999
6 · The paper itself

Abstract

'Naked' nucleic acid vaccines are potentially useful candidates for the treatment of patients with cancer, 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 microg. 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.

Indexed as

AnimalsAntibody FormationApoptosisB-LymphocytesCancer VaccinesCD8-Positive T-LymphocytesColonic NeoplasmsDendritic CellsEnhancer Elements, GeneticInjections, IntramuscularMiceMice, Inbred BALB CPlasmidsPromoter Regions, GeneticRecombinant ProteinsReverse Transcriptase Polymerase Chain ReactionCancer VaccinesRecombinant ProteinsRNA-Dependent RNA Polymerase

Identifiers

PMID10395329
PMCPMC1976249
OpenAlexW1535836957

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.