Investigating genetic modifications to enhance L1CAM-CAR T cell migration in solid tumors in a 3D bioprinted neuroblastoma model

Our findings reveal a key limitation of murine xenograft models, which are widely used as the gold standard for preclinical CAR T cell testing. The lack of conservation between the human and murine SELPLG proteins likely accounts for the discrepancy between enhanced <i>in vitro</i> migration of SELPLG-deficient L1CAM-CAR T cells and their lack of improved efficacy in the mouse model. This underscores the need for more predictive human-relevant models to better preclinically evaluate CAR T cell function.

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Publication Details

Journal
Frontiers in Immunology
Published
2025-11-27
DOI
https://doi.org/10.3389/fimmu.2025.1677361
Primary Topic
CAR-T cell therapy research
Type
article
Field-Weighted Citation Impact
0.00

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article

Investigating genetic modifications to enhance L1CAM-CAR T cell migration in solid tumors in a 3D bioprinted neuroblastoma model

Anton George Henssen, Tobias Lam, Silke Schwiebert, Kathleen Anders et al.
Frontiers in Immunology
CAR-T cell therapy research
article

Investigating genetic modifications to enhance L1CAM-CAR T cell migration in solid tumors in a 3D bioprinted neuroblastoma model

Anton George Henssen, Tobias Lam, Silke Schwiebert, Kathleen Anders, Annette Künkele, Maria Stecklum, Marvin Jens, Johannes H. Schulte, Laura Grunewald, Lena Andersch, Angelika Eggert, Lutz Kloke, Kathy Astrahantseff, Viola Hollek, Filippos Klironomos, Michael Launspach, Nils Blüthgen, Kerstin Haase, Anika Winkler, B. Jung
article en

Abstract

Our findings reveal a key limitation of murine xenograft models, which are widely used as the gold standard for preclinical CAR T cell testing. The lack of conservation between the human and murine SELPLG proteins likely accounts for the discrepancy between enhanced <i>in vitro</i> migration of SELPLG-deficient L1CAM-CAR T cells and their lack of improved efficacy in the mouse model. This underscores the need for more predictive human-relevant models to better preclinically evaluate CAR T cell function.

Frontiers in ImmunologyVol. 16
German Cancer Research Center (DE), Heidelberg University (DE), Humboldt-Universität zu Berlin (DE), German Cancer Society (DE), BioTez (Germany) (DE), Helios Hospital Berlin-Buch (DE), Berlin Heart (Germany) (DE)
Deutsche Forschungsgemeinschaft
Openalex Percentile: Top 49%
CAR-T cell therapy research
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