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Scientists report today in the New England Journal of Medicine* that 11 of 13 patients with hairy cell leukemia, a cancer of the immune system, had complete remissions after receiving adequate treatment with the recombinant immunotoxin BL22. A recombinant immunotoxin is an antibody that has been bioengineered to recognize and directly deliver a deadly toxin to tumors, in this case, hairy cell leukemia cells. According to the authors, this week's results are particularly impressive because the patients, all of whom failed previous chemotherapy, were treated in a Phase I clinical trial, an early study designed primarily to determine how to administer a drug, not cure the disease. Pastan said the two other patients in the study who received adequate treatment had partial remissions, and they continue to receive BL22. "We expected that some patients would respond to the treatment," said Ira Pastan, M.D., a senior author on the paper and leader of the National Cancer Institute's immunotoxin therapy group. "But we didn't imagine in our wildest dreams that almost all of the patients would go into complete remission. Half of the patients went into complete remission after a single cycle of treatment, and that was exciting to see." Pastan said BL22, developed in the laboratory jointly with NCI scientists Robert J. Kreitman, M.D., and David J. FitzGerald, Ph.D., was licensed over a year ago to AlbaPharm, Inc., of Rockville, Md. The company, in collaboration with Pastan's group, is now planning a larger clinical trial with the immunotoxin that will involve hairy cell leukemia patients from throughout the country. Hairy cell leukemia, or HCL, is diagnosed in about 700 Americans each year, accounting for about 2 percent of all leukemias. This week's results were highlighted last April during a presentation at the annual meeting of the American Association for Cancer Research. According to Kreitman, the principal investigator of the clinical trial and a senior author on the paper, BL22 is made by cloning portions of antibodies to portions of a toxin secreted by the bacteria Pseudomonas aeruginosa. "Recombinant DNA techniques allow cloning part of the antibody and part of the toxin to make a smaller recombinant immunotoxin that gets into the tumor faster and reduces the toxicity to the body," said Kreitman. The antibody portion of BL22 specifically binds to the CD22 receptor, which is found in abundance on the surface of many types of leukemia cells. CD22 is also found, in lower amounts, on the surface of normal B cells. Therefore, it seems likely that BL22 would bind to and destroy both leukemic cells and normal B cells. Because stem cells––the progenitors of normal B cells––do not have CD22, any B cells lost in the short-term treatment should be replaced by the patient's untouched stem cells. And, in fact, Kreitman and his colleagues did not detect a decrease in normal B cells of patients. Kreitman added, "Malignant stem cells–– the progenitors of the leukemic cells--may be CD22-positive as well and be lost, too. But only further follow-up will determine if this is correct." Therefore, it is thought that this treatment may not only clear the body of malignant circulating cells but may remove the source of the cells, the malignant stem cells. The most serious side effect of BL22 immunotoxin treatment was a decrease in platelet and red blood cell counts. This decrease was associated with the clotting and breaking up of red blood cells in the kidney, which can cause kidney failure. However, both patients experiencing the side effect completely recovered and had complete remissions of HCL. Using a modified method of BL22 administration, this side effect was not detected in many patients treated later in the study. It is possible that the BL22 immunotoxin will prove to be useful in treating more than just hairy cell leukemia. The Phase I trial includes patients with other types of leukemia and, while Kreitman and his colleagues saw the most dramatic response in HCL, a significant benefit was seen in chronic lymphocytic leukemia. These leads are being followed up by the researchers. "The hairy cell leukemia cells have more CD22 receptors and therefore respond faster and more thoroughly than the other cancers being investigated," Kreitman explained. *The article is titled, "High Complete Remission Rate in Chemotherapy-Resistant Classic or Variant Hairy Cell Leukemia Induced by the Anti-CD22 Recombinant Immunotoxin BL22," published in the July 26, 2001, issue of the New England Journal of Medicine. The authors are: Robert J. Kreitman, Wyndham H. Wilson, Karen Bergeron, Miranda Raggio, Maryalice Stetler-Stevenson, David FitzGerald, and Ira Pastan. Posted Date: Wednesday, July 25, 2001 | About Mary Stolfa | Our Mission | Newsletter | Volunteer | Beauty Parlor | News Articles | Clinical Trials | Other Resources for Cancer Information | Nutrition | Acknowledgement, Awards & Public Acclaim | Foundation Projects | MSCF Products | | Return Home | Fundraisers | Donations | Wall of Honor | Stories of Hope | Information on Specific Cancers (A-M) | Cancer Issues | Contact Us | Site Index | |
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