A patient derived xenograft repository capturing clinical and molecular heterogeneity of large B-cell lymphoma
Large B-cell lymphomas (LBCLs) are a clinically and molecularly diverse group of malignancies with a rapidly evolving therapeutic landscape that has introduced new areas of clinical need such as post-CD19 chimeric antigen receptor T (CART19) progression. Patient derived xenograft (PDX) models are an important tool for mechanistic studies and preclinical evaluation of new therapies and can be generated from a variety of clinical contexts that capture tumor-intrinsic resistance mechanisms. We therefore undertook a comprehensive effort to generate PDX models that encompass the molecular landscape of LBCLs and include important clinical scenarios for new drug development. Here we describe the first 48 models within this publicly available repository, capturing the transcriptional and genetic subsets of LBCL. These models also include 23 generated from post-CART progression biopsies which reproduce patterns of progression driven by <i>CD19</i> mutation or expression loss, as well as tumor cell-intrinsic CART19 resistance that we validate <i>in vivo</i>.
Authors
- Priya Lakra
- Laura K. Hilton (ORCID: https://orcid.org/0000-0002-6413-6586)
- David W. Scott (ORCID: https://orcid.org/0000-0002-0435-5947)
- Jason R. Westin (ORCID: https://orcid.org/0000-0002-1824-2337)
- Swaminathan P. Iyer (ORCID: https://orcid.org/0000-0002-1646-813X)
- Jared Henderson (ORCID: https://orcid.org/0000-0002-5121-5234)
- R. Eric Davis (ORCID: https://orcid.org/0000-0001-7311-0065)
- Frederick Hagemeister
- Hun Ju Lee
- Kevin Bowman
- Sydney Parsons (ORCID: https://orcid.org/0009-0009-2223-2121)
- Alma María Rodríguez
- Estela Rojas
- Dai Chihara
- Francisco Vega
- Luis Malpica
- Kotaro Arita
- Michael R Green
- Luis Fayad
- Giorgio Inghirami
- Christopher R Flowers
- Sattva Neelapu
- Paolo Strati
- Aneela Abedin
- Griffin Rost
- Loretta Nastoupil
- Haopeng Yang
Institutions
- NewYork–Presbyterian Hospital (US)
- The University of Texas MD Anderson Cancer Center (US)
- Cornell University (US)
- New York Hospital Queens (US)
- Spinal Cord Injury BC (CA)
- Presbyterian Hospital (US)
- Weill Cornell Medicine (US)
- The University of Texas Health Science Center at Houston (US)
Publication Details
- Journal
- bioRxiv (Cold Spring Harbor Laboratory)
- Published
- 2026-01-20
- DOI
- https://doi.org/10.64898/2026.01.19.700406
- Primary Topic
- CAR-T cell therapy research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Leukemia and Lymphoma Society
- University of Texas MD Anderson Cancer Center
- National Cancer Institute
- Moonshot Research and Development Program