Gene-modified stem cells help protect bone marrow from toxic side effects of chemotherapy

May 21, 2011

Although chemotherapy is used to kill cancer cells, it can also have a strong toxic effect on normal cells such as bone marrow and blood cells, often limiting the ability to use and manage the chemotherapy treatment. Researchers at Fred Hutchinson Cancer Research Center reported at today's annual meeting of the American Society of Gene and Cell Therapy in Seattle that one possible approach to reduce this toxic effect on bone marrow cells is to modify the cells with a gene that makes them resistant to chemotherapy.

Hans-Peter Kiem, M.D., a member of the Hutchinson Center's Clinical Research Division, and colleagues Jennifer Adair, Ph.D., a research associate in the Clinical Research Division, and Maciej Mrugala, M.D., Ph.D., M.P.H., a neuro-oncololgist at the Seattle Cancer Care Alliance and the University of Washington, presented data from a clinical trial in which bone marrow stem cells from patients with were removed and modified with a retrovirus vector to introduce the chemotherapy-resistant gene. The cells were then re-infused into the patients. In the trial, which was designed to evaluate safety and feasibility, patients were safely administered gene-modified blood stem cells that persisted for more than one year and did not show any apparent harmful effects.

This approach was first attempted in patients with a terminal form of called glioblastoma. Currently, median survival for glioblastoma patients is just 12 to 15 months. The prognosis for glioblastoma patients is poor not only because no curative treatment is available but because doctors cannot effectively use the treatment that does exist. Glioblastoma cells make a large amount of a protein called MGMT that makes them resistant to chemotherapy, so doctors use a second drug, called benzylguanine, to knock down MGMT and make the tumor cells susceptible to the chemotherapy. However, this potent one-two punch is not limited to the brain . Benzylguanine also disables MGMT in normal blood and , leaving them also susceptible to the effects of chemotherapy. The effects on patients' blood and bone marrow can be pronounced and often limit the ability to effectively administer the chemotherapy.

"Our initial results are encouraging because our first patient is still alive and without evidence of disease progression almost two years after diagnosis," Kiem said.

The results of the trial suggest the administration of the modified cells represent a safe method for protecting marrow and from the harmful effects of chemotherapy in brain tumor patients. Future clinical trials will be done to determine whether this combination chemotherapy will also improve the survival of patients with glioblastoma.

Related Stories

Recommended for you

Stem cell therapy attacks cancer by targeting unique tissue stiffness

July 26, 2017
A stem cell-based method created by University of California, Irvine scientists can selectively target and kill cancerous tissue while preventing some of the toxic side effects of chemotherapy by treating the disease in a ...

Understanding cell segregation mechanisms that help prevent cancer spread

July 26, 2017
Scientists have uncovered how cells are kept in the right place as the body develops, which may shed light on what causes invasive cancer cells to migrate.

Study uncovers potential 'silver bullet' for preventing and treating colon cancer

July 26, 2017
In preclinical experiments, researchers at VCU Massey Cancer Center have uncovered a new way in which colon cancer develops, as well as a potential "silver bullet" for preventing and treating it. The findings may extend to ...

Compound shows promise in treating melanoma

July 26, 2017
While past attempts to treat melanoma failed to meet expectations, an international team of researchers are hopeful that a compound they tested on both mice and on human cells in a petri dish takes a positive step toward ...

Study may explain failure of retinoic acid trials against breast cancer

July 25, 2017
Estrogen-positive breast cancers are often treated with anti-estrogen therapies. But about half of these cancers contain a subpopulation of cells marked by the protein cytokeratin 5 (CK5), which resists treatment—and breast ...

Breaking the genetic resistance of lung cancer and melanoma

July 25, 2017
Researchers from Monash University and the Memorial Sloan Kettering Cancer Center (MSKCC, New York) have discovered why some cancers – particularly lung cancer and melanoma – are able to quickly develop deadly resistance ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.