Developing a 3D B Cell Lymphoma Culture System to Model Antibody Therapy

Area of Science:

• Oncology
• Cell Biology
• Biomedical Engineering

Background:

• Diffuse large B cell lymphoma (DLBCL) is a common non-Hodgkin lymphoma (NHL) with a significant unmet need for effective therapies in refractory or relapsed cases.
• The tumor microenvironment (TME) is crucial for DLBCL progression, involving complex interactions between malignant cells, cancer-associated fibroblasts (CAF), and tumor-associated macrophages (TAM).
• Primary DLBCL cells have poor survival in vitro when cultured alone, necessitating models that recapitulate the TME for accurate therapeutic evaluation.

Purpose of the Study:

• To develop a novel 3D spheroid co-culture system that replicates key components of the DLBCL TME.
• To enable in vitro testing of current and novel DLBCL therapies by improving primary DLBCL cell survival ex vivo.
• To create a platform for studying therapeutic responses, including antibody-directed phagocytosis.

Main Methods:

• Generation of lymphoid-like fibroblasts from adipocyte-derived stem cells (ADSC).
• Co-culture of ADSC-derived stroma with lymphocytes (B cells) and monocyte-derived macrophages (MDM) in 2D and 3D spheroid systems.
• Assessment of DLBCL cell viability and interaction with the 3D TME model.
• Evaluation of the system's utility for testing immunotherapeutic antibodies like rituximab.

Main Results:

• Confirmed interaction between lymphocytes and ADSC-derived stroma, with or without MDM, in both 2D and 3D cultures.
• Demonstrated improved viability of DLBCL cells when cultured within the 3D spheroid system compared to 2D monocultures.
• Validated the 3D system as a platform for studying antibody-directed phagocytosis using rituximab.

Conclusions:

• A novel 3D spheroid co-culture system effectively mimics key components of the DLBCL TME.
• This system supports primary DLBCL cell survival ex vivo, offering a valuable platform for therapeutic research.
• The model has potential for testing novel therapeutics targeting cellular constituents of the TME, such as CAF and TAM.