LLS RESEARCH PROGRESS
Progress is being supported by the Research Grants Program. For example:
Targeted Therapies are designed to kill cancer cells but spare healthy cells, unlike today’s
standard treatments that kill cells non-discriminately and can produce debilitating and lifethreatening side-effects. “Targeted therapies” can be developed as researchers discover the
molecules that cause particular cancers and/or allow those cancers to spread. These wonder drugs
include Gleevec®, a pill for chronic myeloid leukemia patients that was developed by Brian
Druker MD of Oregon Health and Science University with LLS research funding.
Now two LLS-funded researchers and their colleagues have developed a new drug that is showing
good early results for patients with stubborn lymphomas. Margaret Shipp MD of the DanaFarber Cancer Institute in Boston had previously shown that a molecule called SYK is essential
to the survival of aggressive lymphoma cells and that a drug that inhibits SYK can kill most of
these lymphomas in the laboratory. A clinical trial of the R788 drug was developed for
relapsed/refractory B-cell lymphoma patients and led by Jonathan Friedberg MD of the
University of Rochester's James P. Wilmot Cancer Center. The trial entered patients in
Rochester, Boston and across the country and nearly half of these patients showed real
improvement. After further trials, his new, twice-a-day pill may offer patients with recurrent small
lymphocytic lymphoma, chronic lymphocytic leukemia and diffuse large B-cell lymphoma an
important option as they progress through various treatments.
New Diagnostic Tests can be used to more accurately distinguish blood cancer subtypes and help
patients receive the best possible, individualized treatment from among all those available. This
became possible when scientists recently used novel high-throughput methods to catalogue the
entire DNA sequence and identified most genes in human cells. Scientists can measure entire
patterns of gene and protein activity (genomics, proteomics) and thereby recognize “molecular
cancer signatures”. Not only can this information help choose from among available treatments,
but it can be used to identify new molecular targets for safer and more effective treatments.
Vivian Oehler MD of the Fred Hutchinson Cancer Research Center and her colleagues have
developed a method for the early detection of a common means by which chronic myeloid
leukemia cells escape chemotherapy. The new test detects a specific genetic mutation that
apparently leads to resistance to the targeted drugs Gleevec, Sprycel, and Tasigna, and detects this
mutation far earlier than today’s standard tests. By minutely partitioning cancer cell samples prior
to genetic testing, it can find a few mutated molecules in as many as 100,000 molecules. This new
strategy may aid in the early detection of relapse in any patient whose cancer cells carry a
recognized mutation and could allow doctors to change treatments as soon as possible, when
patients are most likely to benefit.
Immunotherapies can help a patient’s own immune system fight their cancer. Our immune
systems normally fight infections by attacking infected cells, but can attack cancer cells too.
Unfortunately, the immune systems of blood cancer patients contain increasing numbers of
cancerous immune cells and are further weakened by radiation and drug treatments, especially the
high-dose treatments used before potentially curative stem cell transplants. In fact, infections are a
major cause of death for transplant patients as it takes 12 – 24 months for a patient’s immune
system to recover post-transplant.
LLS-funded Carl June MD at the University of Pennsylvania and his colleagues developed a
new “immunotherapy” that can rebuild a patient’s immune system within 2 months of stem cell
transplantation, using engineered immune cells called “T-cells”. In 2006, Dr. June and LLS-funded
Aaron Rapaport MD of the University of Maryland reported positive results for a preliminary
study in myeloma patients who were able to mount immune responses soon after transplants. In
2007, Dr. June and his LLS co-funded colleague, Stephen Schuster MD, also at the University
of Pennsylvania, reported promising early results for engineered T-cells given to follicular
lymphoma patients after standard drug therapy. Additional studies are underway in myeloma,
lymphoma and leukemia patients. As positive results accumulate, it seems that a patient’s immune
system can be strengthened enough to also respond to anti-cancer vaccines. Combined with new
targeted drugs, these immunotherapies may soon offer safe and effective alternatives to toxic
chemotherapies.
Progress is being supported by the Therapy Acceleration Program. For example:
Academic Concierge Division: Four pilot projects were initiated in FY08. One contract supports
the reformulation of an FDA-approved drug from a topical to an oral form for a clinical trial in
leukemia and lymphoma (LLS investigator, Aaron Schimmer MD, PhD, FRCPC of the
Ontario Cancer Institute). Two TAP contracts support medicinal chemistry and preclinical
development of a new treatment for acute myelogenous leukemia patients (LLS investigator,
John Bushweller, PhD of the University of Virginia), The fourth contract supports the
production of clinical vaccine materials that will be used to prevent post-transplant
lymphoproliferative disease in organ transplant recipients (LLS investigator, Michael Caligiuri,
MD at The Ohio State University Comprehensive Cancer Center).
Clinical Trials Division: LLS entered into a partnership with Cleveland Clinic Taussig Cancer
Institute in Ohio to create a Clinical Trial Center for Hematologic Malignancies. The Center will
enroll a total of 100 to 150 lymphoma patients in at least six Phase I and II clinical trials over the
next three years. The Center initiated its first LLS clinical trial (“A Phase I Trial of the
Combination of Everolimus (RAD001) and Bortezomib (VELCADE) for Relapsed or Refractory
Indolent and Mantle Cell Non-Hodgkin's Lymphoma”) in May 2008. The total operating cost for
the Center is $1.2 million over three years.
Biotechnology Accelerator: As of June 30, 2008, product development contracts have been
signed with four companies. LLS is funding Anjin Group, Inc., a Massachusetts biotechnology
company, to help develop the company’s lead product, a targeted-toxin therapy for acute
myelogenous leukemia. Early research on this approach had been previously reviewed and
supported by grants from the LLS Translational Research Program. MannKind Corporation, a
California-based biotechnology company, is receiving LLS funds to support efforts to develop
drugs to treat patients with T-cell forms of leukemia or lymphoma. The drug target is novel,
existing compounds are highly specific and potent, the patient population is significant and there is
a clear regulatory pathway to clinical trials for this new treatment approach. Aegera Therapeutics,
a Montreal-based company, is being supported to conduct a clinical trial testing a novel therapy
designed to treat chronic myelogenous leukemia (CLL) and follicular lymphoma. LLS is also
funding Memgen, LLC, a Dallas-based biotechnology company that will open a clinical trial to
test a novel treatment for CLL patients whose leukemic cells are lacking a portion of chromosome
17 and/or are refractory or resistant to standard chemotherapies.