Abstract

A phase 1 trial with immunotoxin BL22 that targets CD22 on B cell malignancies has been completed and a maximum tolerated dose established as 40 micrg/kg given I.V. every other day for 3 doses. The therapeutic responses in this trial were extraordinary with more than half the patients with drug resistant Hairy Cell Leukemia going into complete remission. A phase 2 trial in HCL has been approved and is open to accrual. A phase 1 trial with BL22 in pediatric malignancies in collaboration with D. Alan Wayne has been planned and should open soon. Two phase 1 trials with immunotoxin SS1P that targets ovarian cancers, mesotheliomas and pancreatic cancers are now open. In one trial SS1P is given continuously for 10 days. In the other trial SS1P is given by bolus injection every other day times three. Several minor responses but no major responses have been observed. The MTD has not yet been reached. Phase 2 trials with LMB2, an immunotoxin targeting CD25 have also been planned in patients with CLL and CTCL and should be open late in 2003.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Division of Basic Sciences - NCI (NCI)
Type
Intramural Research (Z01)
Project #
1Z01BC010020-08
Application #
6950625
Study Section
(LMB)
Project Start
Project End
Budget Start
Budget End
Support Year
8
Fiscal Year
2003
Total Cost
Indirect Cost

  Institution

Name
Basic Sciences
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

Du, Xing; Beers, Richard; Fitzgerald, David J et al. (2008) Differential cellular internalization of anti-CD19 and -CD22 immunotoxins results in different cytotoxic activity. Cancer Res 68:6300-5
Onda, Masanori; Beers, Richard; Xiang, Laiman et al. (2008) An immunotoxin with greatly reduced immunogenicity by identification and removal of B cell epitopes. Proc Natl Acad Sci U S A 105:11311-6
Sampson, John H; Akabani, Gamal; Archer, Gerald E et al. (2008) Intracerebral infusion of an EGFR-targeted toxin in recurrent malignant brain tumors. Neuro Oncol 10:320-9
Sampson, John H; Brady, Martin L; Petry, Neil A et al. (2007) Intracerebral infusate distribution by convection-enhanced delivery in humans with malignant gliomas: descriptive effects of target anatomy and catheter positioning. Neurosurgery 60:ONS89-98;discussion ONS98-9
Sampson, John H; Raghavan, Raghu; Brady, Martin L et al. (2007) Clinical utility of a patient-specific algorithm for simulating intracerebral drug infusions. Neuro Oncol 9:343-53
Sterman, Daniel H; Recio, Adri; Carroll, Richard G et al. (2007) A phase I clinical trial of single-dose intrapleural IFN-beta gene transfer for malignant pleural mesothelioma and metastatic pleural effusions: high rate of antitumor immune responses. Clin Cancer Res 13:4456-66
Sampson, John H; Raghavan, Raghu; Provenzale, James M et al. (2007) Induction of hyperintense signal on T2-weighted MR images correlates with infusion distribution from intracerebral convection-enhanced delivery of a tumor-targeted cytotoxin. AJR Am J Roentgenol 188:703-9
Ise, Tomoko; Kreitman, Robert J; Pastan, Ira et al. (2006) Sandwich ELISAs for soluble immunoglobulin superfamily receptor translocation-associated 2 (IRTA2)/FcRH5 (CD307) proteins in human sera. Clin Chem Lab Med 44:594-602
Onda, Masanori; Nagata, Satoshi; Ho, Mitchell et al. (2006) Megakaryocyte potentiation factor cleaved from mesothelin precursor is a useful tumor marker in the serum of patients with mesothelioma. Clin Cancer Res 12:4225-31
Hassan, Raffit; Remaley, Alan T; Sampson, Maureen L et al. (2006) Detection and quantitation of serum mesothelin, a tumor marker for patients with mesothelioma and ovarian cancer. Clin Cancer Res 12:447-53

Showing the most recent 10 out of 19 publications