---
title: "Design rules for a modular peptide-tag adaptor BRiDGE CAR T cell system"
id: "biorxiv-8-development-and-design-rules-for-a-modular-human-peptide-tag-adaptor-car-t-cell"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-8-development-and-design-rules-for-a-modular-human-peptide-tag-adaptor-car-t-cell"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.10.21.760864v1?rss=1"
published_at: "2026-10-22T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Design rules for a modular peptide-tag adaptor BRiDGE CAR T cell system
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-8-development-and-design-rules-for-a-modular-human-peptide-tag-adaptor-car-t-cell
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.10.21.760864v1?rss=1)
- **Published At:** 2026-10-22T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- The study presents a modular CAR platform named **BRiDGE CAR** that uses peptide-tag adaptors to control and redirect **CAR T cell** activity. - Investigators tested how CAR hinge length, adaptor format and adaptor valency affected activity; these structural variables determined functional outcomes in vitro and in xenograft models. - A medium-length CAR hinge plus a full-length, bivalent adaptor produced the most consistent, potent antitumour activity across the tested tumour antigens and xenograft models. - In repeated antigen challenge experiments, CD33-directed **BRiDGE CAR** T cells preserved a less-differentiated phenotype compared with direct CD33-targeting CAR T cells, according to the authors. - In vivo, BRiDGE CAR T cells persisted during periods when the adaptor was withdrawn and recovered antitumour activity when the adaptor was re-administered. - Adding **IL-18** armouring to BRiDGE CAR T cells improved tumour control at a reduced CAR T-cell dose, as reported by the study team. - The authors state they identified key design parameters that allow antigen targeting and CAR T cell function to be modified independently within a modular system. - The article is a preprint and has not been peer reviewed; the authors are employees of Biosceptre and report related patent interests and company development efforts.
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Alexander Haide Joechner Biosceptre (Aust) Pty Ltd * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Alexander%2BHaide%2BJoechner%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Joechner%20AH&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AAlexander%2BHaide%2BJoechner%2B) * [ORCID record for Alexander Haide Joechner](http://orcid.org/0009-0008-7039-5382 "Open in new tab") Melanie Mach Biosceptre (Aust) Pty Ltd * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Melanie%2BMach%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Mach%20M&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this 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"Open in new tab") Daniel Barton Biosceptre (Aust) Pty Ltd * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Daniel%2BBarton%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Barton%20D&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3ADaniel%2BBarton%2B) Ziduo Li Biosceptre (Aust) Pty Ltd * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Ziduo%2BLi%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Li%20Z&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AZiduo%2BLi%2B) * [ORCID record for Ziduo Li](http://orcid.org/0009-0002-3358-3524 "Open in new tab") * For correspondence: cindy.li@biosceptre.com * [Abstract](https://www.biorxiv.org/content/10.64898/2026.10.21.760864v1)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_art/node:5892960/1) * [Info/History](https://www.biorxiv.org/content/10.64898/2026.10.21.760864v1.article-info)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_info/node:5892960/1) * [Metrics](https://www.biorxiv.org/content/10.64898/2026.10.21.760864v1.article-metrics)[](https://www.biorxiv.org/panels_ajax_tab/article_tab_metrics/node:5892960/1) * [Supplementary material](https://www.biorxiv.org/content/10.64898/2026.10.21.760864v1.supplementary-material)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_data/node:5892960/1) * [ Preview PDF](https://www.biorxiv.org/content/10.64898/2026.10.21.760864v1.full.pdf+html)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_pdf/node:5892960/1) ![Loading](https://www.biorxiv.org/sites/all/modules/contrib/panels_ajax_tab/images/loading.gif) ## Abstract CAR T cells are highly effective in haematological malignancies, but limited post-infusion control and tumour antigen heterogeneity remain major challenges. Modular CAR systems address these limitations using interchangeable adaptor molecules (AM) to control CAR T cell engagement and redirect targeting toward different antigens, yet the design principles underlying effective modular function remain undefined. We present our modular platform, BRiDGE CAR, and systematically examine how CAR and adaptor configuration influence activity. BRiDGE CAR activity was influenced by CAR hinge length and adaptor format and valency; a medium-length hinge combined with a full-length, bivalent adaptor supported potent activity across multiple tumour antigens and consistently controlled tumour growth across the tested xenograft models. During repeated antigen challenge, CD33-directed BRiDGE CAR T cells retained less-differentiated phenotypes than direct CD33-targeting CAR T cells. In vivo, BRiDGE CAR T cells persisted during adaptor withdrawal and regained antitumour activity upon adaptor re-administration, while IL-18 armouring enhanced tumour control at a reduced CAR T-cell dose. We identified key design parameters governing rules for adaptor-mediated CAR activity, with antigen targeting and CAR T cell function remaining independently modifiable, establishing BRiDGE CAR as a flexible and controllable modular platform. ### Competing Interest Statement All authors are employees of Biosceptre (Aust) Pty Ltd and hold unexercised share options in Biosceptre International Limited. A.H.J. and Z.L. are named inventors on patent applications relating to the BRiDGE CAR platform. Biosceptre is developing the BRiDGE CAR platform described in this study. ## Funder Information Declared Biosceptre (Aust) Pty Ltd Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. bioRxiv and medRxiv thank the following for their generous financial support: > The Chan Zuckerberg Initiative, Cold Spring Harbor Laboratory, the Sergey Brin Family Foundation, California Institute of Technology, Centre National de la Recherche Scientifique, Fred Hutchinson Cancer Center, Imperial College London, Massachusetts Institute of Technology, Stanford University, The University of Edinburgh, University of Washington, and Vrije Universiteit Amsterdam. [Donate to openRxiv ](https://www.zeffy.com/en-US/donation-form/donate-to-make-a-difference-10981) [ Back to top](https://www.biorxiv.org/content/10.64898/2026.10.21.760864v1?rss=1#page) [ Previous](https://www.biorxiv.org/content/10.64898/2026.09.17.751883v2 "New cerebellar nuclei evolve through diversification of excitatory progenitors")[Next ](https://www.biorxiv.org/content/10.64898/2026.10.21.758783v1 "AgamOBP4-targeted drug repurposing identifies novel mosquito repellent scaffolds") Posted October 22, 2026. [ Download PDF](https://www.biorxiv.org/content/10.64898/2026.10.21.760864v1.full.pdf) Print/Save Options [Download PDF](https://www.biorxiv.org/content/biorxiv/early/2026/10/22/2026.10.21.760864.full.pdf)Full Text & In-line FiguresXML [More Info](https://www.biorxiv.org/about/FAQ#PrintOptions "More Information on Print/Save Options") [Supplementary Material ](https://www.biorxiv.org/content/10.64898/2026.10.21.760864v1.supplementary-material) [ Email](https://www.biorxiv.org/ "Email this Article") [ Share](https://www.biorxiv.org/) Development and design rules for a modular human peptide-tag adaptor CAR T cell system Alexander Haide Joechner, Melanie Mach, Michael Yeh, Riya Mehta, Taliah Khoury, Ecem Kurangil, Jinting Yan, Daniel Barton, Ziduo Li bioRxiv 2026.10.21.760864; doi: https://doi.org/10.64898/2026.10.21.760864 This article is a preprint and has not been certified by peer review [[what does this mean?](https://www.biorxiv.org/about/FAQ#unrefereed)]. 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