Work

Expanded and activated marrow-infiltrating lymphocytes exhibit potent antimyeloma activity against autologous multiple myeloma cells

Year: 2025

Type: article

Abstract: • Developed a method to expand eMILs from MM patient bone marrow. • Culture enriched CD8 + T cells, reduced Tregs, MDSCs, and NK cells. • Expanded eMILs were ∼80 % central memory T cells with tumor-homing ability. • eMILs showed potent cytotoxicity against autologous MM tumor cells. Adoptive immunotherapy represents a promising treatment for multiple myeloma (MM), relying on the availability of sustainable tumor-specific cytotoxic T cells. This study generated potent ex vivo expanded and activated marrow-infiltrating lymphocytes (eMILs) from MM patients and evaluated their immunologic characteristics and cytotoxic potential. MILs were expanded using anti-CD3/CD28 beads in the presence of IL-2, IL-7, and IL-15. The expansion rate, proportions of effector cells (including CD4 + T cells, CD8 + T cells, natural killer cells, and memory T cells), and the functional capacity of eMILs were assessed over 2 weeks of culture. Co-culturing MILs with anti-CD3/CD28 beads and cytokines resulted in substantial expansion and activation of MILs during the 14-day culture period. The eMILs displayed an increased proportion of CD8 + T cells and a high prevalence of central memory T cells (Tcm; > 80 %), with minimal presence of myeloid-derived suppressor cells or regulatory T cells. Compared to expanded peripheral blood lymphocytes, eMILs demonstrated potent cytotoxicity against target MM cells, particularly CD138 + primary MM cells from autologous patients. These findings suggest that MILs derived from the bone marrow (BM) of MM patients can be expanded and activated to exhibit enhanced antigen specificity for CD138 + MM cells. Furthermore, eMILs may induce sustained cytotoxic effects due to their high proportion of Tcms. In conclusion, as a unique subset of T cells shaped by the BM microenvironment, MILs show promise as a novel immunotherapeutic approach for MM.

Source: Translational Oncology

DOI: 10.1016/j.tranon.2025.102475