AN INNOVATIVE APPROACH FOR MULTIPLE MYELOMA TREATMENT
ETABLISSEMENT FRANCAIS DU SANG - 06/03/2021
Multiple myeloma (MM) is the second most prevalent hematological cancer after non Hodgkin’s lymphoma (10-12%) and is responsible for 2% of cancer death. In MM, the bone marrow microenvironment (constituted by mesenchymal stromal cells, “MSC") is pivotal to the establishment and progression of the pathology and MM plasma cell growth. MM-MSC are abnormal and overexpress Toll like receptor 4 (TLR 4). EFS researchers have found that TLR 4 is overexpressed on MM MSCs and its activation promotes the crosstalk with MM cells in enhancing pro tumoral factors. EFS proposes a novel therapeutic approach for MM comprising a TLR 4 specific antagonist combined to chemotherapy treatment
• First drug targeting the bone marrow MSCs and tumor microenvironment in MM • Combination treatment suggests lower doses of conventional treatment agents used leading to less side effects and less therapy costs • TLR4 specific antagonist can distinguish pathological and healthy microenvironment • Treatment compatible with induction or consolidation phases • Treatment compatible with any kind of route of administration (oral, sublingual, dermal, transdermal...)
The research team highlighted a higher TRL4 gene expression in MM MSCs than MSCs from healthy donors. At clinical levels, TLR4 expression in MM MSCs evolves in parallel with the disease stage. Thus, the EFS research team has evaluated the therapeutic efficacy of a TLR4 antagonist combined or not with conventional treatment in vitro and in vivo. The selective TLR4 inhibitor alone and to a greater extent, its combination with current MM drugs, specifically reduced the MM MSC ability to support growth of MM cells and delayed the development of MM in the Vk *MYC mouse model. These results confirm TLR4 as an attractive therapeutic target of the pathological microenvironment in MM.