Pan-B-Lineage Targeting with Adapter CAR-T Cells Controls Antigen-Heterogeneous Lymphoma

Authors

Krost, S., Mast, A.-S., Atar, D., Kristmann, B., Scheuermann, S., Seitz, C. M.

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 CD38low 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.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 19 Sep 2026.

Stats

1-terrible, 9-excellent. How would you rate this preprint? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.