Debate is raging as to which medical system provides the best patient care. By looking at current health systems in the United States, Canada, Europe and the rest of the world the obvious answer is that no system is perfect. The same applies to medical research. The U.S/European Alliance was established with the intent to combine the best of the U.S. and Europe’s research. The Alliance addresses five major CLL research themes: New Drugs, CLL-Stromal Interactions, Antibodies and Minimal Residual Disease, Gene and Vaccine Therapy and Transplantation/Immune Reconstitution.
On January 30th and 31st a meeting in Houston, Texas took place marking the second year of activity of the U.S./European Alliance. There was an atmosphere of mutual respect and energy as researchers shared milestones of their grant projects, discussed existing collaborations and had the opportunity to meet new potential collaborators.
One of the strengths of the Alliance is the flexibility in responding to new opportunities and the ability to reassign resources where applicable. It is important that the CLL Global funded projects will lead to a cure in the quickest way possible. In keeping with this mission, a few modifications are being implemented. New researchers have joined the Alliance and were in attendance at the January meeting.
The theme of Antibodies and Minimal Residual Disease is being revised. There are standardized methods of measuring minimal residual disease in blood and bone marrow but not for measuring total tumor burden in the lymph nodes, spleen and other areas where CLL cells reside. Developing technology has been difficult. The advancement of new monoclonal antibodies is largely controlled by the pharmaceutical industry, giving very little flexibility to investigators attempting to initiate newer approaches. Going forward, CLL Global’s support of antibodies and minimal residual disease research will be incorporated into other areas of research.
If the MRD and antibodies theme is being economized, what replaces it? Through the outstanding generosity of CLL Global Research Foundation donors, we have now established a Genetics theme. Researchers in this new working group informed the January attendees of what they will each bring to the table to advance CLL genetic research.
Drs. Carlo Croce and George Calin have been responsible for the development of key cancer regulatory genes called microRNAs (miRs). Data presented on their latest studies show the importance of miR genes in regulating CLL cells and of the association of miRs with prognosis.
Dr. Lynn Abruzzo, a new Alliance member, and Dr. Stephan Stilgenbauer, a former member of the antibodies and MRD group, are investigating different chromosomes where genetic material is lost and how this affects various sub-groups of CLL patients. Dr. Ulf Klein, another new addition to the Alliance, presented a concept of abnormalities on IL-4r gene in blocking differentiation of the CLL cells. These individuals are leaders in the development of applied genetic strategies in CLL. The new Genetics group should be fully funded and operational by mid 2010.
Analysis of genetic material is complicated. Dr. Kevin Coombes, a bioinformatician, is bringing a different perspective and a helpful hand to the Alliance. He has brought to our attention the need for hi-tech tools to analyze CLL genetics, especially when the information needing to be analyzed comes from multiple researchers. The technology which can lead to rapid connections between the research being conducted by investigators within the U.S./European Alliance is becoming available. Development of a semantic database in a disease like CLL would represent a major step forward in providing a platform to ask research questions in the whole of cancer.
The two themes of New Drugs and CLL-Stromal Interaction have worked very closely over the last two years. There is now a clearer understanding of the complex messages being delivered from stromal cells, blood vessels and T-lymphocytes which surround the CLL cells and sustain their survival. The CLL-Stromal Interaction group has clarified some of the questions of the complex microenvironment and created an opportunity for testing in conjunction with investigators exploring new drug approaches. Dr. Peng Huang, a member of the New Drugs group, has discovered an essential nutrient for CLL cell survival which is provided by the stromal cells. He is evaluating a drug which can obstruct this process.
Major efforts are being exerted to force CLL cells and immune cells to interact. The Gene and Vaccine Therapy and Transplant/Immune Reconstitution groups are working together on this objective through various approaches. New molecules called chimeric antigen receptors (CARs) are being developed with one end of the molecule attaching to the immune cell and the other to an antigen or protein on the surface of the CLL cell. This interaction enables immune cells to recognize CLL cells as cancerous. Dr. Laurence Cooper of MD Anderson in conjunction with Drs. Tom Kipps and Gianpietro Dotti are developing unique CARs for CLL therapy. Hopefully one of these clinical trials will be activated this year and the second in 2011.
A CLL Global funded clinical trial using expanded T-lymphocytes with technology developed by Dr. Carl June has been enrolling patients at MD Anderson and University of Pennsylvania. Results are still preliminary, however it has been demonstrated that CLL specific immune reactions can be generated in cord blood cells with expanded T-cells. Dr. June’s technology is already proving beneficial for CLL patients.
A key element of the U.S./European Alliance illustrated at our recent meeting is true collegiality among the investigators, all of whom are interested in and supportive of each other’s research. Having the world’s CLL thought leaders join together brings unparalleled expertise and passion to the meeting. It is an honor for me to be apart of this. The Alliance is a unique model which will accelerate the promise of taking CLL from a generally controllable disease to a disease which can be cured within the next few years.
To see pictures from the Alliance meeting please [click the slideshow.]
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