Evidence map›Paper›PMID 38532017›Full record

ArticleCommunications medicine2024

A CD25-biased interleukin-2 for autoimmune therapy engineered via a semi-synthetic organism.

Jerod L Ptacin, Lina Ma, Carolina E Caffaro, Nicole V Acuff, Kristine Germar, Peter Severy, Yanyan Qu, Jose-Luis Vela, Xinming Cai, Kristine M San Jose and 14 more

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

Article in Communications medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
1.2field-weighted citation impact, top 22% 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

5 citing papers in PubMed, 5 citations in OpenAlex.

  1. Regulatory T cells: From Foxp3 to tolerance-inducing therapies.The Journal of investigative dermatology · 2026
    Review
  2. Taming immune responses to AAV gene therapy by programmed in vivo Treg expansion.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Article
  3. Review
  4. Article
  5. Article
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

24 authors at 2 institutions in 1 country.

Jerod L PtacinSynthorx, a Sanofi Company, 11099 N. Torrey Pines Rd. Suite 190, La Jolla, CA, 92037, USA.ORCID http://orcid.org/0000-0001-7573-1754
Lina MaSynthorx, a Sanofi Company, 11099 N. Torrey Pines Rd. Suite 190, La Jolla, CA, 92037, USA.
Carolina E CaffaroSynthorx, a Sanofi Company, 11099 N. Torrey Pines Rd. Suite 190, La Jolla, CA, 92037, USA.
Nicole V AcuffSynthorx, a Sanofi Company, 11099 N. Torrey Pines Rd. Suite 190, La Jolla, CA, 92037, USA.
Kristine GermarSanofi, 350 Water St., Cambridge, MA, 02141, USA.
Peter SeverySanofi, 350 Water St., Cambridge, MA, 02141, USA.
Yanyan QuSanofi, 350 Water St., Cambridge, MA, 02141, USA.
Jose-Luis VelaSanofi, 350 Water St., Cambridge, MA, 02141, USA.
Xinming CaiSanofi, 350 Water St., Cambridge, MA, 02141, USA.
Kristine M San JoseSynthorx, a Sanofi Company, 11099 N. Torrey Pines Rd. Suite 190, La Jolla, CA, 92037, USA.
Hans R AerniSynthorx, a Sanofi Company, 11099 N. Torrey Pines Rd. Suite 190, La Jolla, CA, 92037, USA.
David B ChenSynthorx, a Sanofi Company, 11099 N. Torrey Pines Rd. Suite 190, La Jolla, CA, 92037, USA.
Ean EscheSynthorx, a Sanofi Company, 11099 N. Torrey Pines Rd. Suite 190, La Jolla, CA, 92037, USA.
Taylor K IsmailiSynthorx, a Sanofi Company, 11099 N. Torrey Pines Rd. Suite 190, La Jolla, CA, 92037, USA.
Rob HermanSynthorx, a Sanofi Company, 11099 N. Torrey Pines Rd. Suite 190, La Jolla, CA, 92037, USA.
Yelena PavlovaSynthorx, a Sanofi Company, 11099 N. Torrey Pines Rd. Suite 190, La Jolla, CA, 92037, USA.
Michael J PenaSynthorx, a Sanofi Company, 11099 N. Torrey Pines Rd. Suite 190, La Jolla, CA, 92037, USA.
Jasmine NguyenSynthorx, a Sanofi Company, 11099 N. Torrey Pines Rd. Suite 190, La Jolla, CA, 92037, USA.
Lilia K KoriazovaSynthorx, a Sanofi Company, 11099 N. Torrey Pines Rd. Suite 190, La Jolla, CA, 92037, USA.
Laura K ShawverSynthorx, a Sanofi Company, 11099 N. Torrey Pines Rd. Suite 190, La Jolla, CA, 92037, USA.
Ingrid B JosephSynthorx, a Sanofi Company, 11099 N. Torrey Pines Rd. Suite 190, La Jolla, CA, 92037, USA.ORCID http://orcid.org/0009-0009-7348-9138
Jill MooneySynthorx, a Sanofi Company, 11099 N. Torrey Pines Rd. Suite 190, La Jolla, CA, 92037, USA.
Mark PeakmanSanofi, 350 Water St., Cambridge, MA, 02141, USA.
Marcos E MillaSynthorx, a Sanofi Company, 11099 N. Torrey Pines Rd. Suite 190, La Jolla, CA, 92037, USA. marcos@samsaracap.com.ORCID http://orcid.org/0000-0001-6446-2085
Torrey Pines Institute For Molecular Studies · USSanofi (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundNatural cytokines are poorly suited as therapeutics for systemic administration due to suboptimal pharmacological and pharmacokinetic (PK) properties. Recombinant human interleukin-2 (rhIL-2) has shown promise for treatment of autoimmune (AI) disorders yet exhibits short systemic half-life and opposing immune responses that negate an appropriate therapeutic index.

methodsA semi-synthetic microbial technology platform was used to engineer a site-specifically pegylated form of rhIL-2 with enhanced PK, specificity for induction of immune-suppressive regulatory CD4 + T cells (Tregs), and reduced stimulation of off-target effector T and NK cells. A library of rhIL-2 molecules was constructed with single site-specific, biorthogonal chemistry-compatible non-canonical amino acids installed near the interface where IL-2 engages its cognate receptor βγ (IL-2Rβγ) signaling complex. Biorthogonal site-specific pegylation and functional screening identified variants that retained engagement of the IL-2Rα chain with attenuated potency at the IL-2Rβγ complex.

resultsPhenotypic screening in mouse identifies SAR444336 (SAR'336; formerly known as THOR-809), rhIL-2 pegylated at H16, as a potential development candidate that specifically expands peripheral CD4+ Tregs with upregulation of markers that correlate with their suppressive function including FoxP3, ICOS and Helios, yet minimally expands CD8 + T or NK cells. In non-human primate, administration of SAR'336 also induces dose-dependent expansion of Tregs and upregulated suppressive markers without significant expansion of CD8 + T or NK cells. SAR'336 administration reduces inflammation in a delayed-type hypersensitivity mouse model, potently suppressing CD4+ and CD8 + T cell proliferation.

conclusionSAR'336 is a specific Treg activator, supporting its further development for the treatment of AI diseases.

Identifiers

PMID38532017
PMCPMC10966033
OpenAlexW4393200097

What OpenQuestion holds

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Registered trials

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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.