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Updated: Oct 7, 2025
Manufacturing Chimeric Antigen Receptor CAR T Cells for Adoptive Immunotherapy
Published on: December 17, 2019
A BAFF ligand-based CAR-T cell targeting three receptors and multiple B cell cancers
Derek P Wong1, Nand K Roy2, Keman Zhang2
1Department of Pathology, Case Western Reserve University, Cleveland, OH, USA.
Abstract:
B cell-activating factor (BAFF) binds the three receptors BAFF-R, BCMA, and TACI, predominantly expressed on mature B cells. Almost all B cell cancers are reported to express at least one of these receptors. Here we develop a BAFF ligand-based chimeric antigen receptor (CAR) and generate BAFF CAR-T cells using a non-viral gene delivery method. We show that BAFF CAR-T cells bind specifically to each of the three BAFF receptors and are effective at killing multiple B cell cancers, including mantle cell lymphoma (MCL), multiple myeloma (MM), and acute lymphoblastic leukemia (ALL), in vitro and in vivo using different xenograft models. Co-culture of BAFF CAR-T cells with these tumor cells results in induction of activation marker CD69, degranulation marker CD107a, and multiple proinflammatory cytokines. In summary, we report a ligand-based BAFF CAR-T capable of binding three different receptors, minimizing the potential for antigen escape in the treatment of B cell cancers.
Insights
Researchers developed a novel BAFF CAR-T therapy targeting B cell cancers. This therapy effectively eliminates various B cell malignancies by binding multiple receptors, reducing the risk of treatment resistance.
Area of Science:
- Immunology
- Oncology
- Biotechnology
Background:
- B cell-activating factor (BAFF) and its receptors (BAFF-R, BCMA, TACI) are crucial for B cell survival and are expressed on most B cell cancers.
- Targeting these receptors offers a potential therapeutic strategy for B cell malignancies.
Purpose of the Study:
- To develop and evaluate a BAFF ligand-based chimeric antigen receptor (CAR) T-cell therapy for B cell cancers.
- To assess the efficacy and specificity of BAFF CAR-T cells against multiple B cell malignancies.
Main Methods:
- Generation of BAFF CAR-T cells using non-viral gene delivery.
- In vitro and in vivo assessment of BAFF CAR-T cell binding specificity to BAFF receptors.
- Evaluation of BAFF CAR-T cell-mediated killing of B cell cancer cell lines and xenograft models.
- Analysis of immune activation markers (CD69, CD107a) and cytokine production upon co-culture.
Main Results:
- BAFF CAR-T cells demonstrated specific binding to BAFF-R, BCMA, and TACI.
- Effective in vitro and in vivo killing of mantle cell lymphoma (MCL), multiple myeloma (MM), and acute lymphoblastic leukemia (ALL) cells.
- BAFF CAR-T cell co-culture induced T-cell activation markers and pro-inflammatory cytokines.
Conclusions:
- A novel BAFF CAR-T cell therapy targeting multiple BAFF receptors has been developed.
- This approach shows promise for treating B cell cancers by minimizing antigen escape.
- BAFF CAR-T cells offer a potential new strategy for overcoming treatment resistance in B cell malignancies.
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