---
title: "Pan-B-Lineage Control of Antigen-Heterogeneous Lymphoma Using Adapter CAR-T Cells"
id: "biorxiv-1-pan-b-lineage-targeting-with-adapter-car-t-cells-controls-antigen-heterogeneous"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-1-pan-b-lineage-targeting-with-adapter-car-t-cells-controls-antigen-heterogeneous"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.09.12.751171v1?rss=1"
published_at: "2026-09-18T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Pan-B-Lineage Control of Antigen-Heterogeneous Lymphoma Using Adapter CAR-T Cells
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-1-pan-b-lineage-targeting-with-adapter-car-t-cells-controls-antigen-heterogeneous
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.09.12.751171v1?rss=1)
- **Published At:** 2026-09-18T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- Antigen heterogeneity and antigen-negative relapse limit durability of CAR-T therapies in B-lineage malignancies. - The study evaluates the **Adapter CAR-T (AdCAR-T)** platform, which redirects engineered T cells to selected surface antigens via biotinylated adapter molecules (AMs). - AMs derived from an in-house tafasitamab biosimilar (anti-**CD19**), commercial rituximab (anti-**CD20**), and an in-house daratumumab biosimilar (anti-**CD38**) mediated potent, antigen-specific AdCAR-T cytotoxicity in vitro. - Single-antigen targeting with AdCAR-T cells led to selection of antigen-negative tumor populations in the model tested. - Simultaneous targeting of **CD19**, **CD20**, and **CD38** controlled a defined heterogeneous Burkitt lymphoma model in vitro and produced sustained tumor control in vivo. - Exposure to CD38-directed AMs caused selective loss of the CD38+ AdCAR-T cell population consistent with fratricide; a CD38-low population survived and retained cytotoxic function. - The findings support combinatorial AdCAR-T targeting as a flexible pan-B-lineage approach to address existing antigen heterogeneity in B-cell malignancies and justify further development of antibody-derived AM combinations. - Competing interests and funding: University Children’s Hospital Tuebingen received research support from Miltenyi Biotec; one author (CMS) receives unrelated funding from Miltenyi Biotec and is co-inventor on an Adapter CAR patent. Specific experimental details, quantitative results, and protocol parameters were not reported in the summary abstract.
## Clinical Analysis & Structured Key Points
Pan-B-Lineage Targeting with Adapter CAR-T Cells Controls Antigen-Heterogeneous Lymphoma | bioRxiv Skip to main content New Results Pan-B-Lineage Targeting with Adapter CAR-T Cells Controls Antigen-Heterogeneous Lymphoma View ORCID Profile Simon Krost , Anna-Sophia Mast , Daniel Atar , Beate Kristmann , Sophia Scheuermann , Christian Martin Seitz doi: https://doi.org/10.64898/2026.09.12.751171 Simon Krost 1 Hopp Children's Cancer Center Heidelberg (KiTZ); Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Simon Krost Anna-Sophia Mast 2 University Childrens Hospital Tuebingen Find this author on Google Scholar Find this author on PubMed Search for this author on this site Daniel Atar 2 University Childrens Hospital Tuebingen Find this author on Google Scholar Find this author on PubMed Search for this author on this site Beate Kristmann 2 University Childrens Hospital Tuebingen Find this author on Google Scholar Find this author on PubMed Search for this author on this site Sophia Scheuermann 2 University Childrens Hospital Tuebingen Find this author on Google Scholar Find this author on PubMed Search for this author on this site Christian Martin Seitz 1 Hopp Children's Cancer Center Heidelberg (KiTZ); Find this author on Google Scholar Find this author on PubMed Search for this author on this site For correspondence: christian.seitz{at}kitz-heidelberg.de Abstract Info/History Metrics Supplementary material Preview PDF Abstract Antigen heterogeneity and antigen-negative relapse represent major limitations to durable CAR-T cell efficacy in B-lineage malignancies. We previously developed the Adapter CAR-T cell (AdCAR-T) platform, which enables flexible redirection of engineered T cells to distinct surface antigens through biotinylated adapter molecules (AMs). In this study, AMs generated from an in-house-produced tafasitamab biosimilar (anti-CD19), commercial rituximab (anti-CD20), and an in-house-produced daratumumab biosimilar (anti-CD38) mediated potent, antigen-specific AdCAR-T cell cytotoxicity. While single-antigen targeting resulted in the selection of antigen-negative tumor populations, simultaneous targeting of CD19, CD20, and CD38 effectively controlled a defined heterogeneous Burkitt lymphoma model in vitro and induced sustained tumor control in vivo . Selective loss of the CD38 + AdCAR-T cell population after CD38-directed AM exposure was consistent with fratricide; however, the surviving CD38 low population retained cytotoxic activity. These findings establish combinatorial AdCAR-T cell targeting as a flexible pan-B-lineage strategy for addressing pre-existing antigen heterogeneity and support further development of antibody-derived AM combinations for B-cell malignancies. Competing Interest Statement The University Childrens Hospital Tuebingen received research support from Miltenyi Biotec GmbH under a collaborative research agreement. CMS receives research funding from Miltenyi Biotec GmbH unrelated to the present work and is a coinventor on patent WO2018078066A1 concerning Adapter CAR technology. The other authors declare no competing interests. Funder Information Declared Deutsche Forschungsgemeinschaft , 411791562 Miltenyi Biotec (Germany), https://ror.org/00qhe6a56 , Collaborative research agreement Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license . Back to top Previous Next Posted September 18, 2026. Download PDF Supplementary Material Email Thank you for your interest in spreading the word about bioRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. You are going to email the following Pan-B-Lineage Targeting with Adapter CAR-T Cells Controls Antigen-Heterogeneous Lymphoma Message Subject (Your Name) has forwarded a page to you from bioRxiv Message Body (Your Name) thought you would like to see this page from the bioRxiv website. Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions. Share Pan-B-Lineage Targeting with Adapter CAR-T Cells Controls Antigen-Heterogeneous Lymphoma Simon Krost , Anna-Sophia Mast , Daniel Atar , Beate Kristmann , Sophia Scheuermann , Christian Martin Seitz bioRxiv 2026.09.12.751171; doi: https://doi.org/10.64898/2026.09.12.751171 Share This Article: Copy Citation Tools Pan-B-Lineage Targeting with Adapter CAR-T Cells Controls Antigen-Heterogeneous Lymphoma Simon Krost , Anna-Sophia Mast , Daniel Atar , Beate Kristmann , Sophia Scheuermann , Christian Martin Seitz bioRxiv 2026.09.12.751171; doi: https://doi.org/10.64898/2026.09.12.751171 Citation Manager Formats BibTeX Bookends EasyBib EndNote (tagged) EndNote 8 (xml) Medlars Mendeley Papers RefWorks Tagged Ref Manager RIS Zotero Tweet Widget Facebook Like Google Plus One Subject Areas All Articles Animal Behavior and Cognition (8010) Biochemistry (18733) Bioengineering (14878) Bioinformatics (44394) Biophysics (22589) Cancer Biology (19717) Cell Biology (26897) Clinical Trials (138) Developmental Biology (13964) Ecology (21005) Epidemiology (2067) Evolutionary Biology (25436) Genetics (16162) Genomics (23498) Immunology (18693) Microbiology (42451) Molecular Biology (18056) Neuroscience (93420) Paleontology (700) Pathology (2977) Pharmacology and Toxicology (5093) Physiology (8111) Plant Biology (15998) Scientific Communication and Education (2095) Synthetic Biology (4559) Systems Biology (10233) Zoology (2390)
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