# Building clinically faithful ex vivo indolent lymphoma models for personalized therapy

> **NIH NIH R21** · RESEARCH INST OF FOX CHASE CAN CTR · 2022 · $214,186

## Abstract

Project Summary
Due to their indolent nature, few cell lines or animal models have been established for chronic lymphocytic
leukemia (CLL) and follicular lymphoma (FL) compared to other types of cancer. The primary goal of this
proposal is to establish an ex vivo indolent lymphoma (iNHL) model that mimics the tumor in vivo
microenvironment with faithful readouts of drug sensitivity/ resistance to enable personalized medicine. The
central hypothesis is that an ex vivo model with tumor microenvironment (TME) mimicry would make iNHL
behave physiologically and provide a clinical faithful model for drug testing. Guided by our preliminary data, the
objective will be achieved by the following two specific aims: 1) To refine and build ex vivo iNHL models
that will best support tumor cell in vivo behaviors; 2) To validate the models by correlating modeled
drug response with patients’ clinical response and/or mutation profiles. In the first aim, optimized ex vivo
iNHL models will be created by transducing bone marrow fibroblasts (BMF) with B-cell growth factors,
mimicking different cell types found in the tumor milieu in the lymph nodes. Subsequent co-culture-induced
changes in cellular behaviors will be measured including cell proliferation and adhesion that are rarely
measured in the absence of suitable iNHL models. We then aim to demonstrate that the model is clinically
relevant and potentially useful. We will correlate individual modeled cellular response with the clinical response
and/or mutation profiles for 60 patients using each patient’s tumor cells to build a personalized therapeutic
model. We believe the proposed study is innovative because a practical and clinically faithful personalized
Rx model is currently non-existent for indolent lymphoma. It is anticipated that the eventual model will be
fast, simple, and economical, enabling a personalized drug trial for individual patients. With the model, we seek
to make a stride towards the reality of practicing personalized medicine in the clinic for the benefits of iNHL
patients. Successful completion of the proposed research will deliver the following tangible benefits: 1) Models
which recapitulate the iNHL-TME that enable evaluation of in vivo behaviors of refractory indolent lymphoma,
not currently achievable with the lack of suitable models; 2) Practical (fast, simple, and economical) and
clinically faithful models which may be used to guide individualized therapy selection in the clinic leading to
direct patient benefits; 3) A large number of genetically heterogeneous tumor models which will streamline the
efficiency of future drug development; and 4) A modeling approach potential applicable to other indolent as
well as aggressive lymphomas.

## Key facts

- **NIH application ID:** 10470933
- **Project number:** 5R21CA263415-02
- **Recipient organization:** RESEARCH INST OF FOX CHASE CAN CTR
- **Principal Investigator:** Y. Lynn Wang
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $214,186
- **Award type:** 5
- **Project period:** 2021-08-17 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10470933

## Citation

> US National Institutes of Health, RePORTER application 10470933, Building clinically faithful ex vivo indolent lymphoma models for personalized therapy (5R21CA263415-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10470933. Licensed CC0.

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