Nonclinical Safety Assessment of SBT777101, a CAR-Engineered Regulatory T Cell Therapy for Autoimmune Diseases

Clicks: 25
ID: 328805
2026
Free PDF
Article Quality & Performance Metrics
Overall Quality
Not rated
Combines reader engagement with the AI quality analysis. This article has not been analysed, so there is no overall score — reader engagement is measured and shown alongside.
AI Quality Assessment
Not analyzed
Readership in this journal
Emerging

Ranked #60 of 146 articles by views in toxicological sciences : an official journal of the society of toxicology

Most read Least read

Bar heights use a square-root scale. Only the 120 most-read articles are drawn; the journal has 146 in total.

Mint this article as an NFT
Not yet minted

Create a permanent, verifiable on-chain record of this article on the Scimatic Network. The NFT is held in your Journament account, and you can withdraw it to your own wallet at any time.

5 SUSD one-off · no wallet required
Sign in to mint
Abstract
Chimeric antigen receptor (CAR)-regulatory T cell (Treg) therapies represent a promising approach for autoimmune diseases, but their nonclinical safety assessment remains challenging due to antigen-, disease-, and species-specific pharmacology that limits the relevance of conventional animal models. SBT777101, a CAR-Treg therapy targeting citrullinated proteins associated with rheumatoid arthritis and hidradenitis suppurativa, was evaluated using a nonclinical strategy centered on in vitro and ex vivo New Approach Methodologies (NAMs) and in vivo studies benchmarked against untransduced polyclonal Tregs which are manufactured identically but lack the CAR and have an established clinical safety record, complemented by immunodeficient mouse studies. We hypothesized that CAR engineering would not destabilize the Treg phenotype or introduce new toxicological liabilities relative to polyclonal Tregs. SBT777101 maintained phenotypic stability under repeated stimulation and pro-inflammatory conditions, produced minimal pro-inflammatory cytokines following activation, and demonstrated immunomodulatory activity comparable to untransduced Tregs. Tissue cross-reactivity and primary cell studies identified limited membrane-associated binding, no evidence of CAR-mediated cytotoxicity or activation in normal human tissues, and no off-target binding by broad protein array screening. Immunosuppressive activity toward natural killer and CD8+ T cell responses was limited and comparable to polyclonal Tregs. Lentiviral integration site analyses demonstrated polyclonal integration profiles without evidence of transformation or abnormal growth in a cytokine- and activation-independent growth assay. This study establishes a combination of in vivo and NAM-based nonclinical safety framework for CAR-Treg therapies and demonstrates that CAR engineering of SBT777101 does not introduce new safety liabilities relative to unmodified polyclonal Tregs. These findings supported progression of SBT777101 into Phase 1 clinical trials and offer a generalizable approach for evaluating the safety of future CAR-Treg therapeutics.
Reference Key
openalex_W7213309621 Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors HERVÉ LEBREC, Jonathan M. Clingan, Anne-Renée Van der Vuurst de Vries, Lauren Mihalcik, Yuchi Honaker, Sara Charmsaz, Seonhwa Dura, Kathryn Hooper, Yuanyuan Xiao, Michelle Blake, Max Fiebiger, Radha Dhayal, Christine Saechao, Alexandre Iannello, Fred Ramsdell, Jeffrey A Bluestone, Josh Beilke
Journal toxicological sciences : an official journal of the society of toxicology
Year 2026
DOI
10.1093/toxsci/kfag125
URL
https://academic.oup.com/toxsci/advance-article-pdf/doi/10.1093/toxsci/kfag125/71103878/kfag125.pdf
Keywords Keywords not found

Citations

No citations found. To add a citation, contact the admin at info@scimatic.org

Comments

No comments yet. Be the first to comment on this article.