Combination Therapy Using Invariant Natural Killer T Cells and Immunomodulatory Drugs in Multiple Myeloma

Abstrakt

Invariant natural killer T cells (iNKTs) are lymphocytes connecting innate and adaptive immunity. iNKTs interact with B cells in all maturation stages through the invariant TCR and CD1d presenting lipid antigens. In progressive multiple myeloma (MM), a cancer of plasma cells, the expression of CD1d is downregulated and iNKT function is affected. However, CD1d can be upregulated by all-trans retinoic acid (ATRA). Lenalidomide (LND) and pomalidomide (PMD) are therapeutic agents enhancing the activity of natural killer (NK) cells in MM patients. Therefore, they might also promote iNKT function.

This work aimed to monitor the effect of LND and PMD on iNKTs and CD1d expression after ATRA application. iNKTs isolated from 7 healthy donors (magnetic selection), were 3x activated using irradiated C1RCD1d cells, α-galactosylceramide and IL-15. During the last activation, LND and PMD were added to iNKTs in concentrations 0.25-5 μM. After 96hrs, the cell number, metabolic activity (measured by AlamarBlue) and the main subsets (measured by flow cytometry using CD45, CD8, CD4) were evaluated. Myeloma cell lines were cultured 48hrs with 0.25 - 10µM ATRA and CD1d expression was measured using FACS