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

Maaike V. J. Braham, Monique C. Minnema, Tineke Aarts, Zsolt Sebestyen, Trudy Straetemans, Anna Vyborova, Jurgen Kuball, F. Cumhur Öner, Catherine Robin, Jacqueline Alblas
  • OncoImmunology, February 2018, Taylor & Francis
  • DOI: 10.1080/2162402x.2018.1434465

A novel immunotherapy tested on multiple myeloma cells grown in a 3D bone marrow model

What is it about?

In this study, a 3D bone marrow model was developed, in which bone marrow stem cells were mixed with blood vessel cells. These cells together formed 3D networks, supporting the survival and growth of patients' multiple myeloma cells for up to 28 days. The 3D bone marrow model enabled testing of a novel immunotherapy on the patients' myeloma cells. The immunotherapy cells (TEGs) were engineered and tested from both healthy donors and myeloma patients. The added TEGs were capable of migrating through the 3D model and killing the patients' myeloma cells. No differences were observed comparing the therapies made from healthy donors or myeloma patients. The supporting bone marrow cells were unaffected by the treatment in all conditions.

Why is it important?

Bone marrow niches are microenvironments within the bone marrow, essential in supporting the formation of blood cells and blood cancers such as multiple myeloma. The progression of multiple myeloma depends on signals and cell-cell interactions provided by the surrounding bone marrow. A 3D model of the bone marrow is needed to support the growth of patients' multiple myeloma outside of the body, as these cells cannot be grown independent of the bone marrow. Once established, such a model can be used to better understand interactions between the bone marrow and blood cells, diseases of the bone marrow and the testing of new therapies.

Perspectives

Maaike Braham (Author)
University Medical Center Utrecht

The developed 3D model enables analysis of interactions between individual cells and cell populations. The 3D model also allows the testing of novel (immuno)therapies and research on therapy resistance mechanisms or possible treatment side-effects, within the context of the engineered bone marrow model. Another step for the developed model is to test its usability for the in vitro culture of hematopoietic stem and progenitor cells, that also dependent on the bone marrow niche for their self-renewal and differentiation.

Read Publication

http://dx.doi.org/10.1080/2162402x.2018.1434465

The following have contributed to this page: Maaike Braham