A Patient-Derived Xenograft Repository Capturing Clinical and Molecular Heterogeneity of Large B-cell Lymphoma
Large B-cell lymphomas (LBCL) 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-CART19 progression patient biopsies, which reproduce patterns of progression driven by CD19 mutation or expression loss, as well as tumor cell-intrinsic CART19 resistance that we validated in vivo. SIGNIFICANCE: Here, we describe X-LYMPH (Xenografts of Lymphoma), a publicly available and molecularly annotated PDX repository that captures the heterogeneity of LBCL. X-LYMPH includes models of CAR T-cell resistance, providing a shared foundation for mechanistic research and therapeutic development for lymphomas.
Authors
- Giorgio Inghirami (ORCID: https://orcid.org/0000-0001-5566-0864)
- Fredrick B. Hagemeister
- Francisco Vega (ORCID: https://orcid.org/0000-0001-5956-452X)
- Kotaro Arita (ORCID: https://orcid.org/0000-0003-2838-5961)
- Laura K. Hilton (ORCID: https://orcid.org/0000-0002-6413-6586)
- David W. Scott (ORCID: https://orcid.org/0000-0002-0435-5947)
- Maria Alma Rodriguez (ORCID: https://orcid.org/0000-0002-3564-8697)
- Jason R. Westin (ORCID: https://orcid.org/0000-0002-1824-2337)
- Hun Ju Lee (ORCID: https://orcid.org/0000-0001-7219-5562)
- Haopeng Yang (ORCID: https://orcid.org/0000-0002-3870-2679)
- Swaminathan P. Iyer (ORCID: https://orcid.org/0000-0002-1646-813X)
- Luis Fayad (ORCID: https://orcid.org/0000-0002-1844-5548)
- Loretta J. Nastoupil (ORCID: https://orcid.org/0000-0001-6071-8610)
- Paolo Strati (ORCID: https://orcid.org/0000-0002-7445-1459)
- Jared Henderson (ORCID: https://orcid.org/0000-0002-5121-5234)
- Dai Chihara (ORCID: https://orcid.org/0000-0002-1153-2294)
- Michael Richard Green (ORCID: https://orcid.org/0000-0001-6309-9472)
- R. Eric Davis (ORCID: https://orcid.org/0000-0001-7311-0065)
- Sattva Swarup Neelapu (ORCID: https://orcid.org/0000-0003-1045-4914)
- Luis Malpica (ORCID: https://orcid.org/0000-0002-7082-1846)
- Kevin Bowman
- Christopher R. Flowers (ORCID: https://orcid.org/0000-0002-9524-3990)
- Sydney Parsons (ORCID: https://orcid.org/0009-0009-2223-2121)
- Griffin Rost
- Estela Rojas (ORCID: https://orcid.org/0009-0006-4878-9815)
- Aneela Syeda Abedin (ORCID: https://orcid.org/0009-0008-8373-5622)
- Priya Lakra (ORCID: https://orcid.org/0000-0002-5449-7556)
Institutions
- The University of Texas MD Anderson Cancer Center (US)
- Cornell University (US)
- Spinal Cord Injury BC (CA)
- Presbyterian Hospital (US)
Publication Details
- Journal
- Blood Cancer Discovery
- Published
- 2026-06-24
- DOI
- https://doi.org/10.1158/2643-3230.bcd-26-0005
- Primary Topic
- CAR-T cell therapy research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Leukemia and Lymphoma Society
- National Institutes of Health
- University of Texas MD Anderson Cancer Center