Evidence map›Paper›PMID 41889175›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2026

Enhanced efficacy of a next-generation EEEV self-replicating RNA platform for combination cancer immunotherapies.

Shigeki J Miyake-Stoner, Christian J Maine, Annie C Chou, Gabrielle P Dailey, Darina S Spasova, Christine C Domingo, Jessica Sparks, Gaelle Picarda, H Kim Lyerly, Erika J Crosby and 4 more

Abstract read
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Review
  2. Review
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

14 authors.

Shigeki J Miyake-StonerReplicate Bioscience, San Diego, CA 92121, USA.
Christian J MaineReplicate Bioscience, San Diego, CA 92121, USA.
Annie C ChouReplicate Bioscience, San Diego, CA 92121, USA.
Gabrielle P DaileyDepartment of Surgery, Division of Surgical Sciences, Duke University, Durham, NC 27707, USA.
Darina S SpasovaReplicate Bioscience, San Diego, CA 92121, USA.
Christine C DomingoReplicate Bioscience, San Diego, CA 92121, USA.
Jessica SparksReplicate Bioscience, San Diego, CA 92121, USA.
Gaelle PicardaReplicate Bioscience, San Diego, CA 92121, USA.
H Kim LyerlyDepartment of Surgery, Division of Surgical Sciences, Duke University, Durham, NC 27707, USA; Department of Pathology, Duke University, Durham, NC 27710, USA; Department of Integrative Immunobiology, Duke University, Durham, NC 27706, USA.
Erika J CrosbyDepartment of Surgery, Division of Surgical Sciences, Duke University, Durham, NC 27707, USA; Department of Integrative Immunobiology, Duke University, Durham, NC 27706, USA.
Andrew J GeallReplicate Bioscience, San Diego, CA 92121, USA.
Nathaniel S WangReplicate Bioscience, San Diego, CA 92121, USA.
Zachary C HartmanDepartment of Surgery, Division of Surgical Sciences, Duke University, Durham, NC 27707, USA; Department of Pathology, Duke University, Durham, NC 27710, USA; Department of Integrative Immunobiology, Duke University, Durham, NC 27706, USA.
Parinaz AliahmadReplicate Bioscience, San Diego, CA 92121, USA. Electronic address: paliahmad@replicatebioscience.com.

Funding

Enabling effective anti-tumor immunity from targeted antibodies through dual innate and adaptive immune checkpoint blockade in non-immunogenic cancersR01CA238217 · NCI · DUKE UNIVERSITY · PI HARTMAN, ZACHARY CONRAD · 2020 to 2024
$2.4M
NCI NIH HHS R01 CA238217
6 · The paper itself

Abstract

Self-replicating RNA (srRNA) technology has received its first approval with Kostaive and Emergency Use Authorization for GEMCOVAC COVID-19 vaccines. The effective doses for srRNA vaccines are far lower than for conventional mRNA, as srRNA drives greater protein expression and has attributes of viral vectors that can potentiate immunogenicity. Importantly, srRNA encodes for a viral replicase, frequently derived from non-structural proteins (nsP) from Venezuelan equine encephalitis virus (VEEV), that helps amplify the encoded transgene. nsPs also influence critical cellular processes, including protein translation and processing, inflammation, and autophagy, that can impact downstream performance. Here, we show that a next-generation srRNA vector derived from Eastern equine encephalitis virus, identified from a wider screen of alphaviruses, has high potency in two immunotherapeutic applications, RBI-1000 and RBI-2000. RBI-1000, a multigenic vaccine targeting acquired resistance mutations in breast cancer, was able to elicit antigen-specific immune responses to tumor-associated antigens and neoantigens. In addition, RBI-2000, a combination interleukin-12 and IL-1 receptor antagonist biotherapeutic, resulted in therapeutic levels of protein expression that bolstered anti-tumor immune responses in vivo. Both RBI-1000 and RBI-2000 successfully demonstrated efficacy in preclinical tumor models. These data show the importance of empirically evaluating new srRNA vectors for the development of fit-for-purpose therapies.

Indexed as

Cancer VaccinesEncephalitis Virus, Venezuelan EquineImmunotherapyRNA, ViralAlphavirusAnimalsCell Line, TumorFemaleGenetic VectorsHumansMiceRNA ReplicationCancer VaccinesRNA, ViralalphavirusbiotherapeuticscytokineimmunologyimmunotherapyoncologyRNAself-replicating RNAvaccines

Identifiers

PMID41889175
PMCPMC13102400

What OpenQuestion holds

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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.