Optimisation of a parallel CAR for B-cell lymphoma via ITAM attenuation and target specificity validation

Clicks: 19
ID: 315124
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
Popular

Ranked #45 of 51 articles by views in Clinical & Experimental Immunology

Most read Least read

Bar heights use a square-root scale.

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
INTRODUCTION: Second generation CAR T-cells have transformed the management of B-cell malignancy. However, in vivo functional persistence is often limiting, highlighting a key mechanism of treatment failure. METHODS: We have engineered a parallel (p)CAR platform which delivers dual CD28 and 4-1BB co-stimulation via a co-expressed CAR and chimeric co-stimulatory receptor (CCR). To target CD19, we employed an avidity-optimised FMC63 scFv to direct CAR specificity while utilising an unmodified FMC63 scFv to target the CCR. Here, we describe the late-stage optimisation of this system for Phase 1 clinical evaluation. First, we confirmed that the avidity-optimised scFv lacked off-target specificity. To minimise risk of insertional mutagenesis and immunogenicity respectively, we transitioned from a gammaretrovirus to a third generation lentiviral expression vector and removed epitope tags used to discriminate between CAR and CCR expression. RESULTS: Most strikingly, we found that inactivation of immune tyrosine activation motif 2 and 3 within our pCAR prototype markedly potentiated efficacy in xenograft-bearing NSG mice. Mechanistically, this resulted from increased pCAR T-cell functional persistence and organ infiltration, with enhanced local clearance of malignant B-cells. CONCLUSION: These data set the scene for evaluation of this iteratively honed pCAR candidate in a clinical trial in relapsed/refractory B-cell non-Hodgkin's lymphoma.
Reference Key
openalex_W7162531326 Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Fahima Kausar, Christopher Davis, Daniel Larcombe-Young, Camilla Bove, Farzin Farzaneh, Charlotte Graham, Reuben Benjamin, David M. Davies, John Maher
Are you one of these authors? Claim your profile
Journal Clinical & Experimental Immunology
Year 2026
DOI
10.1093/cei/uxag032
URL
https://doi.org/10.1093/cei/uxag032
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.