Monday, June 25, 2007

Biotest monoclonal antibody development

The monoclonal antibody BT-061, developed by Biotest AG, has demonstrated a very good tolerability profile in a recently completed Phase I clinical study. No relevant clinical side effects were detected in the range of doses tested. In light of existing positive pre-clinical data, the results were in line with expectations.

The development of Biotest's two other monoclonal antibodies is also progressing according to plan. For BT-062, which is being developed to treat the cancer multiple myeloma, clinical testing is set to commence at the Dana Farber Cancer Institute in
Boston and other centres in the USA in the first half of 2008. The development and trial design has been agreed on by the US FDA.

Source: http://www.biotest.de/ww/en/pub/home.cfm

Thursday, June 21, 2007

Allo transplant strategies

Mini-Midi-Maxi? How to harness the graft-versus-myeloma effect and target molecular remission after allogeneic stem cell transplantation

Kröger N.

1Department for Stem Cell Transplantation, University Hospital Hamburg-Eppendorf, Hamburg, Germany.

Allogeneic stem cell transplantation in multiple myeloma after standard myeloablative conditioning induces a high rate of complete remissions, but long-term freedom from disease is achieved in 30-40% of the cases only. The therapeutic effect of allogeneic stem cell transplantation is due to cytotoxicity of high-dose chemotherapy and immune-mediated graft-versus-myeloma effect by donor T cells. Retrospective studies clearly suggest that both (a) reducing the intensity of high-dose chemotherapy by using reduced-intensity or non-myeloablative conditioning regimen or (b) reducing the immunotherapy of donor T cells by using T-cell depletion result in lower treatment-related morbidity and mortality, but also in higher rate of relapse. Therefore, this review will focus on potential strategies of how treatment-related morbidity and mortality might be kept low without an increased risk of relapse and how remission status after transplantation can be enhanced by using the newly established donor immunosystems after allografting as a platform for post-transplant treatment strategies with new drugs (thalidomide, lenalidomide, bortezomib) or immunotherapy (donor lymphocyte infusion, vaccination, tumor-specific T cells) in order to achieve remission on a molecular level, which seems to be a 'conditio sine qua non' to cure myeloma patients.Leukemia advance online publication, 14 June 2007; doi:10.1038/sj.leu.2404775.

Tuesday, June 19, 2007

FISH microelectronics invention

U of A hails 'FISH and chip' cancer test

Invention reduces wait from days to hours

EDMONTON - The University of Alberta has created a miniature lab-on-a-chip that will allow doctors to quickly figure out which chemotherapy will work best for a cancer patient, tailor treatments to them and monitor for relapses.

The hand-held glass chip, created by the U of A team, can perform an important diagnostic test known as FISH on a handheld device.

FISH (fluorescent in situ hybridization) allows oncologists to see abnormalities in cancerous bone marrow, blood or tumours.

The test currently can take days, but the lab on a chip reduces the wait to less than 24 hours, at a fraction of the cost.

"I feel this could be the most important thing that any of us may ever do," said Linda Pilarski, a cancer researcher leading the chip project with Chris Backhouse, an electrical engineering professor. "I'm really excited about it because I've always wanted my work to reach patients."

FISH involves inserting a substance similar to a dye into cancer cells. The dye sticks to certain chromosomes and becomes visible under fluorescent light.

Using the chip, a small, $1,000 machine and a biopsy or blood sample, doctors can see which chromosomes are missing, broken or abnormal and then choose a chemotherapy program or bone-marrow transplant proven to target that form of cancer.

The new test "will have great impact, and quite quickly, on the diagnosis of patients with a broad spectrum of diseases," said Dr. Roderick McInnes, scientific director of the Canadian Institutes of Health Research Institute of Genetics.

"Their FISH and chip technology should allow rapid and inexpensive diagnosis of important genetic changes that can underlie cancer and many developmental and neurological disorders."

Pilarski said the test "heralds the coming of personalized medicine" in which patients get what they need and the health-care system avoids costly trial-and-error attempts to find a treatment that works.

"Physicians urgently need this kind of information to make their treatment decisions," she said.

"The chromosomal analysis is so critical for cancer care because it tells doctors what patient outcome might be, how long they may survive, how bad their disease is likely to be and -- more importantly, perhaps -- it tells them what kinds of therapies the disease will respond to."

The technology will also help doctors catch relapses and tackle the cancer before it gets out of control.

Most patients currently can't get such fine-tuned care. A test to detect chromosomal mutations in certain cancer cells -- such as blood, breast, prostate or colorectal cancers -- can cost about $1,000 and requires a $1-million machine.

As a result, treatments for some cancer patients may not be effective and may cause adverse side-effects.

With their lab-on-a-chip, the tests are cheap -- one slide can hold 10 cell samples instead of one and be studied for $100 -- meaning patients can be monitored over time to detect aggressive new forms of the disease.

Willie Gruber, 48, said the test is crucial to put cancer patients at ease. He was diagnosed with multiple myeloma, a blood cancer, in January 2002 and was told he had four years to live.

But because doctors at the Cross Cancer Institute were researching his type of cancer, he received the expensive, $1,000 chromosome test. He then had to wait three gruelling weeks for the results.

"It's extremely stressful to worry about your future and not know what to expect," said Gruber, noting that doctors debated whether he needed aggressive chemotherapy or a less intense form. "Cancer that's treated earlier gets faster results."

In the end, the test showed his disease wasn't the most virulent form of multiple myeloma, but one that would respond to a bone-marrow transplant.

"It was a great relief," said Gruber, who is now cancer-free.

The lab-on-a-chip technology is so small and so cheap, Pilarski imagines a future where it's used in all medical clinics and hospitals.

"It's a lab anywhere," she said. "This is particularly important for northern or rural patients who can be tested in locations near home instead having to have a sick person make a difficult trip to a hospital in a city or a distant location."

Pilarski said it will likely be five more years before the test becomes widely available. A patent is already pending and the U of A is looking for investors.

The U of A research is being published this month in the journal IET Nanobiotechnology and will be presented at the 11th International Myeloma Workshop, a medical conference to be held in Greece from June 25 to 30.

jsinnema@thejournal.canwest.com

© The Edmonton Journal 2007

Thursday, June 14, 2007

MMRC study: VELCADE(R) with Tipifarnib

The Multiple Myeloma Research Consortium (MMRC) and Emory University today announced the initiation of a multi-center Phase I clinical trial to determine the optimal dose level of VELCADE(R) (bortezomib) for Injection, a proteasome inhibitor, in combination with tipifarnib, a first-in-clinic farnesyl transferase inhibitor, for the treatment of patients with relapsed or refractory multiple myeloma.

The MMRC is the only research model of its kind that brings together 13 leading academic institutions to accelerate the development of novel and combination treatments for multiple myeloma, an incurable cancer of the plasma cell. The MMRC is currently supporting several other clinical trials, including a Phase I study of NPI-0052, a proteasome inhibitor, in collaboration with Nereus Pharmaceuticals; a Phase I study of TKI258, an FGFR3 (fibroblast growth factor receptor 3) inhibitor, in collaboration with Novartis Oncology; and a Phase I study of perifosine, Revlimid(R), and dexamethasone in collaboration with Keryx Biopharmaceuticals.

Entitled "A Phase I Protocol of the Combination Bortezomib and Tipifarnib for Relapsed or Refractory Multiple Myeloma,", MMRC Member Institutions that will enroll patients are City of Hope National Medical Center in Duarte, Calif., Emory University in Atlanta, Ga., and University of Toronto in Toronto, Ontario.

"Encouraging pre-clinical data suggest that VELCADE in combination with tipifarnib may prove to be more active against multiple myeloma cells than either agent alone," said Sagar Lonial, M.D., Associate Professor of Medicine at Emory University's Winship Cancer Institute and the study's principal investigator. Pre-clinical laboratory data suggests that VELCADE and tipifarnib in combination have synergistic activity against multiple myeloma cells.

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