Cellular immunotherapy on primary multiple myeloma expanded in a 3D bone marrow niche model

Area of Science:

• Biomedical Engineering
• Immunology
• Hematology

Background:

• Bone marrow niches are crucial for multiple myeloma (MM) progression.
• Existing models lack the complexity to fully recapitulate the in vivo MM microenvironment.

Purpose of the Study:

• To develop a 3D bone marrow niche model for studying MM.
• To evaluate the efficacy of T cell receptor engineered gamma delta T cells (TEGs) against primary MM cells within this model.

Main Methods:

• Co-culture of mesenchymal stromal cells and endothelial progenitor cells to form a 3D bone marrow niche model.
• Culture of primary CD138+ myeloma cells within the 3D model for up to 28 days.
• Introduction of engineered T cells (TEGs) and mock-transduced T cells to assess anti-myeloma activity.

Main Results:

• The 3D model supported stable outgrowth of primary myeloma cells without genetic drift.
• TEGs demonstrated significant killing of primary myeloma cells in 6 out of 8 donor samples within 24-48 hours.
• The stromal microenvironment remained unaffected by TEG treatment, and no differences were noted between allogeneic and autologous therapies.

Conclusions:

• The developed 3D bone marrow niche model accurately mimics the in vivo environment for MM.
• TEGs show potent anti-myeloma activity in a 3D setting, suggesting potential for clinical application.
• This model facilitates the study of novel immunotherapies, resistance mechanisms, and potential side effects for MM.