The overarching goal of this study was to characterize and develop strategies to harness the immunomodulatory properties of the NF-kB inhibitor IT848 for multiple myeloma (MM) therapy. IT848 is a novel small molecule NF-κB inhibitor that we recently developed as a joint effort with our biotech partner ImmuneTarget Inc. IT848 is a direct inhibitor of … Continued

The goal of this project was to test and characterize a BCMA targeted chimeric antigen receptor (CAR) that we expressed on invariant natural killer T cells (iNKT) for the treatment of multiple myeloma. The advantage of iNKT cells is that they do not cause GvDH, so are a potential “off the shelf” product which means … Continued

This proposal aimed to interrogate at single cell level the tumor microenvironment of CAR-T and TCE treated MM patients to elucidate the immune-mediated causes of resistance, identify potential means to reverse tolerance, and study how genomics might predict which patients should benefit the most from T-cell based therapies.

The project focuses on using the anticancer peptide PNC-27, which targets the p53 pathway, as a potential therapeutic approach for multiple myeloma (MM). While MM with high-risk features like TP53 deletion has poorer outcomes, PNC-27 has shown promising results in cancer cells, including MM, by inducing cell death. Despite the absence of MDM2 on MM … Continued

The project aims to investigate GCK as a therapeutic target for RAS-mutated multiple myeloma (MM), where current treatments are lacking. RAS pathway mutations are common in MM, driving disease progression, yet no RAS inhibitors are clinically available. GCK, a key player in B cell differentiation, has been found critical for MM cell survival and growth, … Continued

The project aims to explore APOBECs as potential therapeutic targets in multiple myeloma (MM). Aim 1 focuses on identifying druggable APOBEC targets by modulating their expression in MM cells and assessing their impact on cellular characteristics. This involves genetic manipulations and functional assays to determine downstream pathways affected by APOBEC activation. Aim 2 investigates the … Continued

Multiple myeloma (MM) is a bone marrow-resident hematologic malignancy of plasma cells and the second most diagnosed blood cancer, after non-Hodgkin lymphoma. Despite the development of myeloma-targeted immunotherapies, MM remains largely incurable. The objective of this research is to evaluate tissue factor (TF, also known as coagulation factor III and CD142) as a new target … Continued

The study aims to enhance the efficacy of chimeric antigen receptor (CAR) T-cell therapy in multiple myeloma (MM) by engineering CAR-T cells to secrete interleukin-12 (IL-12) and an anti-IL-6 single domain antibody (sdAb). While current CAR-T therapies targeting BCMA show promising response rates, median progression-free survival remains short, indicating the need for improved strategies. The … Continued

The rationale of this research translational project has been to investigate the role of glutamine (Gln) and glutamate metabolism as possible new diagnostic tools for MM bone disease in MM patients. The aims of the project were: -Firstly, to check how the alteration of Gln metabolisms induced by MM cells and consequently the Gln addicted … Continued

This research identifies MM-specific bone marrow mesenchymal stromal cells (iMSC) as crucial components of the pro-tumor microenvironment in Multiple Myeloma (MM). These iMSCs support MM cell survival and proliferation and are associated with bone marrow inflammation. Despite successful induction treatment, iMSC presence persists, potentially contributing to therapy resistance and relapse. The study aims to determine … Continued