Monoclonal Antibody Targets, Kills Leukemia Cells

Monoclonal Antibody Targets, Kills Leukemia Cells

 Researchers at the University of California, San Diego Moores Cancer Center have identified a humanized monoclonal antibody that targets and directly kills chronic lymphocytic leukemia (CLL) cells
The findings, published in the online Early Edition of the Proceedings of the National Academy of Sciences on March 25, 2013 represent a potential new therapy for treating at least some patients with CLL, the most common type of blood cancer in the United States.
CLL cells express high levels of a cell-surface glycoprotein receptor called CD44. Principal investigator Thomas Kipps, MD, PhD, Evelyn and Edwin Tasch Chair in Cancer Research, and colleagues identified a monoclonal antibody called RG7356 that specifically targeted CD44 and was directly toxic to cancer cells, but had little effect on normal B cells.
Moreover, they found RG7356 induced CLL cells that expressed the protein ZAP-70 to undergo apoptosis or programmed cell death. Roughly half of CLL patients have leukemia cells that express ZAP-70. Such patients typically have a more aggressive form of the disease than patients with CLL cells that do not express that specific protein.

Previous research by Kipps and others has shown that CLL cells routinely undergo spontaneous or drug-induced cell death when removed from the body and cultured in the laboratory. They found that CLL cells receive survival signals from surrounding non-tumor cells that are present in the lymph nodes and bone marrow of patients with CLL. One of these survival signals appears to be transmitted through CD44. However, when CD44 is bound by the RG7356 monoclonal antibody, it seems to instead convey a death signal to the leukemia cell.
"By targeting CD44, it may be possible to kill CLL cells regardless of whether there are sufficient numbers of so-called 'effector cells,' which ordinarily are required by other monoclonal antibodies to kill tumor cells," said Kipps. "We plan to initiate clinical trials using this humanized anti-CD44 monoclonal antibody in the not-too-distant future."
Co-authors were Suping Zhang, Christina C.N. Wu, Jessie-Farah Fecteau, Bing Cui, Liguang Chen, Ling Zhang, Rongrong Wu, Laura Rassenti, and Fitzgerald S. Lao, Department of Medicine, UCSD Moores Cancer Center; and Stefan Weigand, Roche Diagnostics GmbH, Germany.
Funding for this study came, in part, from the National Institutes of Health (grant PO1-CA081534) and the UC San Diego Moores Cancer Blood Center Research Fund.

Story Source:

The above story is reprinted from materials provided by University of California, San Diego Health Sciences.

Journal Reference:

1. Suping Zhang, Christina C. N. Wu, Jessie-F. Fecteau, Bing Cui, Liguang Chen, Ling Zhang, Rongrong Wu, Laura Rassenti, Fitzgerald Lao, Stefan Weigand, and Thomas J. Kipps. Targeting chronic lymphocytic leukemia cells with a humanized monoclonal antibody specific for CD44. PNAS, March 25, 2013 DOI: 10.1073/pnas.1221841110

Stem Cell Treatment May Become Option to Treat Nonhealing Bone Fractures

Stem Cell Treatment May Become Option to Treat Non healing Bone Fractures

Stem cell therapy enriched with a bone-regenerating hormone, insulin-like growth factor-I (IGF-I), can help mend broken bones in fractures that are not healing normally, a new animal study finds.
The results are being presented at The Endocrine Society's 93rd Annual Meeting in Boston.
A deficiency of fracture healing is a common problem affecting an estimated 600,000 people annually in North America, according to the principal investigator, Anna Spagnoli, MD, associate professor of pediatrics and biomedical engineering at the University of North Carolina at Chapel Hill.
"This problem is even more serious," Spagnoli said, "in children with osteogenesis imperfecta, or brittle bone disease, and in elderly adults with osteoporosis, because their fragile bones can easily and repeatedly break, and bone graft surgical treatment is often not successful or feasible"
Fractures that do not heal within the normal timeframe are called non-union fractures. Using an animal model of a non-union fracture, a "knockout" mouse that lacks the ability to heal broken bones, Spagnoli and her colleagues studied the effects of transplanting adult stem cells enriched with IGF-I. They took mesenchymal stem cells (adult stem cells from the bone marrow) of mice and engineered the cells to express IGF-1. Then they transplanted the treated cells into knockout mice with a fracture of the tibia, the long bone of the leg.
Using computed tomography (CT) scanning, the researchers showed that the treated mice had better fracture healing than did control mice either left untreated or treated only with stem cells. They found that the stem cells enriched with IGF-I became bone cells and helped the cells in the broken bones to repair the fracture, speeding the healing. Compared with controls left to heal on their own, treated mice had more bone bridging the fracture gap, and that new bone was three to four times stronger, according to Spagnoli.
"More excitingly, we found that stem cells empowered with IGF-I restored the formation of new bone in a mouse lacking the ability to repair broken bones. This is the first evidence that stem cell therapy can address a deficiency of fracture repair," she said.
This success in an animal model of fracture non-union, Spagnoli said, "is a crucial step toward developing a stem cell-based treatment for patients with fracture non-unions."
"We envision a clinical use of combined mesenchymal stem cells and IGF-1 similar to the approach employed in bone marrow transplant, in which stem cell therapy is combined with growth factors to restore blood cells," she said. "I think this treatment will be feasible to start testing in patients in a few years."
IGF-I is approved for treatment of children with a deficiency of this hormone, causing growth failure.
The National Institutes of Health supported this study through a NIDDK-NIH R01 grant.

STEM CELL THERAPY.....

Stem Cells Fill Gaps in Bones

 For many patients the removal of several centimetres of bone from the lower leg following a serious injury or a tumour extraction is only the beginning of a long-lasting ordeal. Autologous stem cells have been found to accelerate and boost the healing process. Surgeons at the RUB clinic Bergmannsheil have achieved promising results: without stem cells, it takes on average 49 days for one centimetre of bone to regrow; with stem cells, that period has been reduced to 37 days.
In the past, large bone defect inevitably led to an amputation. Today, the arm or leg is stabilised in an external support, and a transport wire is pulled through the marrow of the intact part of the injured bone. Once the soft tissue surrounding the injury is healed, the surgeons cut the healthy part of the bone into two. The transport wire is affixed to the winches of a ring fixator that is attached around the leg. Using a sophisticated cable-pull system, the previously detached part of the bone is slowly pulled either downwards or upwards along the gap in the bone until it arrives and docks at the other end. During the pulling stage, the periosteum of the bone that had been pulled apart had been continuously stretched. Thus, a periosteum tube is created in the gap behind the relocated portion of the bone. Inside that tube, the new bone can regenerate. This process, however, is extremely tedious and the treatment fails in every firth case.

Processing autologous stem cells in the operating theatre
Surgeons at the RUB clinic Bergmannsheil attempt to optimise the healing process by applying autologous stem cells therapy. Depending on the requirements, stem cells are capable of evolving into different types of tissue cells, including so-called osteoblasts -- cells that are responsible for bone formation. Adult stem cells such as are deployed in the process can be found in the bone marrow of adults. "We harvest them by inserting a hollow needle into the iliac crest," explains PD Dr Dominik Seybold, managing consultant at the clinic.
The stem cells are prepared for application directly on location. Under x-ray control, the surgeons inject six to eight millilitres of the concentrated fluid into the centre of the periosteum tube. X-ray controls are routinely performed to monitor the recovery progress. To date, the RUB physicians have applied this therapy in 20 cases. "This is not enough to be statistically relevant," admits Dr Seybold. Nevertheless, the researchers find the results very encouraging: whilst the bone regeneration process without stem cells used to take 49 days on average, it has been reduced to 37 days on average thanks to the new therapy method. So far, RUB scientists have been treating bone defects with an average length of eight centimetres -- consequently, the patients thus recovered, on average, three months sooner.

Story Source:

The above story is reprinted from materials provided by Ruhr-Universitaet-Bochum, via AlphaGalileo.