Six of the world's most promising clinical investigators have been chosen to receive prestigious 2004 Brian D. Novis Research Grants from the International Myeloma Foundation (IMF) in order to further their research into better treatments, management, prevention and a cure for multiple myeloma, cancer of the bone marrow caused by uncontrolled growth of plasma cells. The awards presentation took place on Saturday, December 6, 2003, during the American Society of Hematology (ASH) 45TH Annual Meeting, one of the largest oncology meetings in the world, in San Diego, CA.
This is the 10th year that the IMF has made grants possible through donations from private individuals. They are awarded annually to doctors and researchers doing work in the field of myeloma. Senior grant recipients receive $80,000 while Junior grant recipients are funded in the amount of $40,000. The 2004 recipients will begin their projects immediately after the first of the year.
Brian Durie, M.D., IMF Chairman of the Board and member of the IMF Scientific Advisory Board bestowed the awards along with Susie Novis, President of the IMF. The 2004 Brian D. Novis Research Grant recipients are the following:
2004 BRIAN D. NOVIS IMF RESEARCH GRANT RECIPIENTS
Dr. Manuel Penichet, M.D., Ph.D, Associate Researcher
"Antibody-avidin Fusion Proteins Targeting the Transferrin Receptor: Potential Therapeutics for the Treatment of MM"
Dr. Penichet hypothesizes that antibody-avidin fusion proteins specific for the transferrin receptor (antiTfR IgG3-AV) can be used alone or in combination with other agents as a novel and effective antiproliferative drug in myeloma. He will first determine the effect of antiTfR IgG3-AV on cell proliferation and apoptosis in myeloma cells. He will then examine the synergistic effect of the combination of antibody-avidin fusion proteins specific for the transferrin receptor with other cytotoxic or sensitizing agents. He then plans to examine the in vivo anti-tumor activity of anti-TfR IgG3-Av alone or combined with another cancer drug in SCID mice bearing human myeloma cells. This represents a new approach to targeted therapy of myeloma.
Dr. Marco Ladetto, Assistant Professor in Hematology
The University of Torino
"The role of cyclooxygenase-2 (COX2) in Multiple Myeloma"
Dr. Ladetto has demonstrated that COX-2 expression is common in myeloma. His preliminary data indicates that nearly 35% of myeloma patients show increased ex-pression of COX-2. He plans to determine the presence of COX-2 expression on a large number of myeloma patients at diagnosis, remission, relapse, and at progression. He will quantify COX-2 mRNA expression and demonstrate COX-2 in the bone marrow by immunochemistry as well as COX-2 expression analysis on assorted cell populations. He will evaluate the prognostic value of COX-2 expression in the outcome of therapy of myeloma.
Dr. Chao-Lan Yu, Assistant Professor
Renewal (second year funding)
"Suppressor of Cytokine Signaling (SOCS): Its Regulation & Potential Implication as a Therapeutic Agent in Multiple Myeloma"
Dr. Yu proposes to continue his studies on the suppression of cytokine signaling through SOCS-1 and SOCS-3 proteins. He has demonstrated that both SOCS-1 and SOCS-3 are present in undetectable levels in two myeloma cell lines. He hypothesizes that the SOCS-3 gene may be hypermethylated in myeloma cells. He has constructed recombinant retroviruses expressing SOCS-1 and SOCS-3 proteins. He plans to continue his investigation into the mechanisms of defective SOCS gene expression and the tumor-suppressing effects of SOCS protein. He will examine the role of hypermethylation of the SOCS genes which are involved in down-regulating cytokine stimulation. He will determine whether SOCS-3 is hypermethylated in myeloma and whether the enforced expression of SOCS proteins has an effect on apoptosis and cell growth.
Dr. Mathias Oelke, Research Associate
Development of artificial antigen presenting cells for adoptive immunotherapy of multiple myeloma"
Dr. Oelke proposes developing artificial antigen presenting cells for adoptive immuno-therapy for myeloma. The major problem is the presence of functional defects associated with autologous dendritic cells in patients with myeloma, as well as the lack of a reproducible and economically viable method for generating antigen-specific T-cells using autologous dendritic cells. His preliminary data indicates that HLA-Ig based artificial Antigen Presenting Complexes (aAPC) can produce antigen specific T-cells. If successful, the use of HLA-Ig based aAPC’s would be a new approach to produce large numbers of specific T-cells for adoptive transfer in myeloma.
Dr. Francesco Piazza, Research Assistant
Venetian Institute of Molecular Medicine, University of Padova
"Roles of CK2 and GSK3 serine-threonine kinases in the regulation of proliferative and survival pathways in MM"
Dr. Piazza will study the roles of CK2 and GSK-3 serine-threonine kinases in the regulation of proliferative and survival pathways in myeloma. CK2 phosphorylates IkB in the C-terminal PEST domain, altering its stability. This PEST domain is also a substrate for calpain-mediated degradation of IkB phosphorylation by CK2. CK2 may facilitate its calpain-dependent degradation in B-lymphocytes. He plans to assess the importance of CK2 directed IkB phosphorylation in myeloma. NF-kB drives transcription of c-myc which is crucial for proliferation in myeloma. He also plans to test whether the NF-kB and CK2 may collaborate in the c-myc pathway and influence myeloma cell proliferation and apoptosis. These findings suggest that CK2 counteracts apoptosis. GSK3b can also modulate NF-kB function. GSK3b has been shown to be essential for the onset of an NF-kB derived antiapoptotic transcriptional program downstream of T1Fk. He aims to study how GSK3b affects NF-kB downstream.
Dr. Hideaki Ishikawa
Investigation of the molecules controlling myeloma cell growth and application for therapy"
This grant is made possible through IMF Japan in memory of Aki Horinouchi. Mr. Horinouchi was the founder of IMF Japan.
Dr. Ishikawa will undertake the investigation of the molecules controlling myeloma cell growth and application for therapy. This research grant is made possible through IMF Japan in memory of Aki Horinouchi. Mr. Horinouchi was the founder of IMF Japan.
The IMF appreciates the evaluation and preparation of critiques of the research grant proposals by Professor Håkan Mellstedt and other IMF Scientific Advisors serving on his committee of reviewers.