The International Myeloma Foundation (IMF) presents its 2020 Research Grant awards at a ceremony held during the 61st annual meeting of the American Society of Hematology (ASH) in December 2019 at Orlando, Florida, USA.
Senior Grant Recipients
Sylvie Hermouet headshot
Sylvie Hermouet, MD, PhD
CRCINA Inserm U1232
Centre de Recherche en Cancérologie et Immunologie Nantes-Angers
Nantes, France
Functional Characterizations of Monoclonal Immunoglobulins from Antigen-Driven MGUS and Myeloma

MGUS and myeloma can be initiated by chronic stimulation by infectious or self antigens. Frequent antigenic targets of monoclonal immunoglobulins from MGUS and myeloma patients include Epstein-Barr virus (EBV, 25% cases), hepatitis C virus (HCV) and lysoglucosylceramide (LGL1) (17% cases). Thus, target antigen reduction, using existing anti-viral drugs or LGL1 reducing therapies, could be useful to treat patients with antigen-driven MGUS or myeloma. To support this approach; we propose to demonstrate that EBV-, HCV- and LGL1- specific mc Igs do exert antibody activity. For this purpose, we will study the capacity of monoclonal immunoglobulins to activate monocytes/macrophages from healthy donors.

Mikhail Nikiforov headshot
Mikhail Nikiforov, PhD
Wake Forest University Health Sciences
Winston-Salem, NC, USA
Leveraging polyamine dependency for treatment of drug-resistant multiple myelomas

Multiple myeloma (MM) accounts for ~10% of all blood cancers. Although current treatments have significantly improved overall survival of multiple myeloma patients, the disease remains incurable largely due to the rapidly emerging drug resistance. Our data demonstrate that drug-resistant multiple myeloma develop a dependency on a high abundance of certain metabolites (polyamines). Moreover, we found an agent that is already approved for use in humans that deprives myeloma cells of that metabolite.In the current proposal we would like to test this agent and another one with a similar mechanism of action in the mouse models of drug-resistant multiple myeloma.

Junior Grant Receipients
Frederico Maura headshot
Francesco Maura, MD
Memorial Sloan Kettering Cancer Centre
New York, NY, USA
Deciphering the Impact of Melphalan on Secondary Malignancy in Multiple Myeloma

High-dose melphalan (HDM) is a widely used, first-line chemotherapeutic agent given to young patients with multiple myeloma (MM). Exposure to HDM has been associated with a higher risk of therapy-related myeloid cancers that often have poor clinical outcomes. We recently described how HDM triggers mutations by looking at the entire genome of patients with MM after HDM therapy. To reduce the risk of secondary myeloid malignancies by identifying efficient prevention and screening strategies, we will investigate the genomic impact of HDM on the initiation and progression of pre-leukemic clonal entities (i.e., CHIP) in patients with MM following HDM therapy

Kim De Veirman headshot
Kim De Veirman, PhD
Hematology and Immunology
Myeloma Center Brussels
Vrije Universiteit Brussel
Brussels, Belgium
Targeting AXL, a putative dormancy regulatory in multiple myeloma

Cancer cell dormancy is a process where the cells cease dividing but survive in a quiescent state. These dormant cancer cells are often untreatable due to drug resistance and are considered as the main reason for relapse of myeloma patients. Previously, we identified AXL as a potential key regulator of myeloma cell dormancy. In this project, we aim to reactivate AXL-expressing cells, hence making them more susceptible to chemotherapy. By the use of AXL-blocking compoiunds in combination with chemotherapy we wish to eradicate residual myeloma cells.

Alexandre Detappe headshot
Alexandre Detappe, PhD
Centre Paul Strauss/ Universite de Strasbourg
Strasbourg, France
A "click ready" Cereblon E3 ligase modulation drug library for fast in vivo evaluation in Multiple Myeloma mouse models

The main limitation of novel small molecule developments after in vitro validation is the optimization of their pharmacokinetic profile. To avoid this task, we developed a high throughput method to conjugate the small molecule to a FDA-approved nanoparticle known for its non-toxicity and well-characterized pharmocokinetic/biodistribution. We will generate a library of 100 novel immunomodulator drugs that will be screened in vitro, enabling the most potent candidates to be easily conjugated onto the macromolecule and quickly translated into Multiple Myeloma mouse models, thus overriding the high cost and time for classical drug pharmacokinetic optimization before clinical testing.

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