Evidence map›Paper›PMID 38261838›Full record

ArticleActa pharmaceutica Sinica. B2024

Cancer immunotherapy with enveloped self-amplifying mRNA CARG-2020 that modulates IL-12, IL-17 and PD-L1 pathways to prevent tumor recurrence.

Ju Chen, Bhaskara Reddy Madina, Elham Ahmadi, Timur Olegovich Yarovinsky, Marie Marthe Krady, Eileen Victoria Meehan, Isabella China Wang, Xiaoyang Ye, Elise Pitmon, Xian-Yong Ma and 3 more

Open access · diamondAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Acta pharmaceutica Sinica. B, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
2.8field-weighted citation impact, top 9% 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

11 citing papers in PubMed, 17 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Review
  5. Advances and Strategies in Enhancing mRNA Cancer Vaccines.Advanced materials (Deerfield Beach, Fla.) · 2025
    Review
  6. Article
  7. Review
  8. Article
  9. Article
  10. Review
  11. 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

13 authors at 2 institutions in 2 countries.

Ju ChenDepartment of Immunology, School of Medicine, University of Connecticut Health Center, Farmington, CT 06030, USA.
Bhaskara Reddy MadinaCaroGen Corporation, Farmington, CT 06030, USA.
Elham AhmadiDepartment of Immunology, School of Medicine, University of Connecticut Health Center, Farmington, CT 06030, USA.
Timur Olegovich YarovinskyCaroGen Corporation, Farmington, CT 06030, USA.
Marie Marthe KradyCaroGen Corporation, Farmington, CT 06030, USA.
Eileen Victoria MeehanDepartment of Immunology, School of Medicine, University of Connecticut Health Center, Farmington, CT 06030, USA.
Isabella China WangDepartment of Immunology, School of Medicine, University of Connecticut Health Center, Farmington, CT 06030, USA.
Xiaoyang YeDepartment of Immunology, School of Medicine, University of Connecticut Health Center, Farmington, CT 06030, USA.
Elise PitmonDepartment of Immunology, School of Medicine, University of Connecticut Health Center, Farmington, CT 06030, USA.
Xian-Yong MaCaroGen Corporation, Farmington, CT 06030, USA.
Bijan AlmassianCaroGen Corporation, Farmington, CT 06030, USA.
Valerian NakaarCaroGen Corporation, Farmington, CT 06030, USA.
Kepeng WangDepartment of Immunology, School of Medicine, University of Connecticut Health Center, Farmington, CT 06030, USA.
UConn Health · USGuangzhou University of Chinese Medicine · CN

Funding

Skeletal, Craniofacial and Oral Biology Training GrantT90DE033006 · NIDCR · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI FRANK C NICHOLS · 2023 to 2026
$2.0M
Control of regulatory T cells by IL-17 in colorectal cancerR01CA262430 · NCI · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI WANG, KEPENG · 2021 to 2025
$1.8M
NCI NIH HHS R01 CA262430NIDCR NIH HHS T90 DE033006
6 · The paper itself

Abstract

Targeting multiple immune mechanisms may overcome therapy resistance and further improve cancer immunotherapy for humans. Here, we describe the application of virus-like vesicles (VLV) for delivery of three immunomodulators alone and in combination, as a promising approach for cancer immunotherapy. VLV vectors were designed to deliver single chain interleukin (IL)-12, short-hairpin RNA (shRNA) targeting programmed death ligand 1 (PD-L1), and a dominant-negative form of IL-17 receptor A (dn-IL17RA) as a single payload or as a combination payload. Intralesional delivery of the VLV vector expressing IL-12 alone, as well as the trivalent vector (designated CARG-2020) eradicated large established tumors. However, only CARG-2020 prevented tumor recurrence and provided long-term survival benefit to the tumor-bearing mice, indicating a benefit of the combined immunomodulation. The abscopal effects of CARG-2020 on the non-injected contralateral tumors, as well as protection from the tumor cell re-challenge, suggest immune-mediated mechanism of protection and establishment of immunological memory. Mechanistically, CARG-2020 potently activates Th1 immune mechanisms and inhibits expression of genes related to T cell exhaustion and cancer-promoting inflammation. The ability of CARG-2020 to prevent tumor recurrence and to provide survival benefit makes it a promising candidate for its development for human cancer immunotherapy.

Indexed as

Cancer immunotherapyCombination therapyIL-12IL-17Oncolytic virusPD-L1T cell exhaustionVirus-like vesicles

Identifiers

PMID38261838
PMCPMC10792965
OpenAlexW4386573515

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.