Ireland Cancer Center of University Hospitals Case Medical Center researchers have recently made great strides in stem cell gene therapy research by transferring a new gene to cancer patients, via their own stem cells, with the ultimate goal of being able to use stronger chemotherapy treatment with less severe side effects.
Under this protocol, MGMT, a drug-resistance gene, is added into purified hematopoietic stem cells to protect these cells from the damage of chemotherapy regimens.
In one of 24 presentations by Ireland Cancer Center researchers at the annual American Society of Hematology meeting, Stanton Gerson, MD, and colleagues presented that eight patients were enrolled on the trial and six were infused with their own stem cells which were engineered to carry the MGMT gene. In three patients, stem cells carrying the gene were identified in their blood or bone marrow. In one patient, stem cells carrying the gene were detected up to 28 weeks after their administration. This significant finding has never been reported before with this gene and drug combination.
¡§This study is the first to show the success of treatment with evidence that stem cells now carry the new gene,¡¨ says Dr. Gerson, Director of the Ireland Cancer Center and Case Comprehensive Cancer Center, who spearheaded the Phase I study along with a team of researchers. ¡§These patients show the success of treatment with evidence that their stem cells now carry the new genes. This is a breakthrough ¡V the first time selection with MGMT has been shown to occur in patients.¡¨
Preclinical animal research, conducted by Dr. Gerson and his colleagues, has shown that the gene G156A-MGMT can provide stem cells with very high levels of drug resistance, compared to normal stem cells not carrying the gene. In the Phase I trial for patients with advanced malignancies, researchers collected peripheral blood stem cells from patients and exposed them to a retrovirus containing the G156A-MGMT gene.
In addition to this promising research, Ireland Cancer Center scientists presented 24 oral and poster presentations at ASH. ¡§The breadth and depth of this innovative hematologic research at the Ireland Cancer Center are outstanding,¡¨ says Alvin Schmaier, MD, Chief of Hematology/Oncology at UHCMC and Case Western Reserve University School of Medicine. ¡§Our faculty is making tremendous advances in these fields which is reflected in their being chosen for oral and poster presentations.¡¨
The presentations include:
- Dr. Hillard Lazarus and colleagues presented significant findings that treatment with Rituximab before transplantation results in cure rate and overall survival in patients undergoing autologous stem cell transplantation for Diffuse Large B-Cell lymphoma.
- Dr. Lazarus and colleagues of the Eastern Cooperative Oncology Group (ECOG) presented data that show that Imatninib (Gleevec) does not change outcomes on patients with Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia.
- Dr. Lazarus presented an assessment of data over 30 years regarding acute leukemia and its management. He found that all avenues lead to stem cell transplantations. His team provided this assessment of a whole host of entities that provide leukemia care.
- Dr. Jonathan Kenyon and colleagues found that normal individuals over age 50 begin to show evidence that genetic mutations are accumulating in marrow stem cells. This finding might be the key underlying the increased risk of anemias, myelodysplastic syndrome and acute leukemia in older individuals.
- Dr. Kevin Bunting¡¦s laboratory gave two important presentations on how intracellular STAT5 (an intracellular signaling protein) influences normal pathologic hematopoiesis (blood cell formation) and stem cell engraftment.
- Dr. Shigemi Matsuyama and colleagues presented a novel way of treating chemotherapy -induced thrombocytopenia (decrease in number of platelets in the blood) using Bax Inhibiting Peptides to rescue the damaged cells.
- Dr. Keith McCrae and colleagues presented that ƒÒ2 glycoprotein is a cofactor in the process that dissolves blood clots through the use of the medical agent tPA.