Abstract

Phase I trials in patients with colon and breast cancer using the anti-LeY solid tumors with immunotoxin LMB-9 are being carried out in collaboration with Dr. Robert Kreitman at NCI and Dr. Peter Hafkemeyer in Freiburg, Germany. LMB-9 is a stable recombinant immunotoxin produced by genetic engineering. Dr. Robert Kreitman has completed a Phase I trial on leukemias and lymphomas with immunotoxin LMB-2 [anti-Tac(Fv)-PE38] that targets the alpha subunit of the IL2 receptor. In this trial, one complete response and many partial responses were observed. Phase II trials are planned in CTCL and CLL. A Phase I trial with immunotoxin (BL22) that targets CD22 present on B-cell malignancies has been completed. Many complete responses in drug resistant Hairy Cell Leukemia were observed. We are planning further trials to determine the safest dose schedule for treatment of HCL, CLL, lymphoma and ALL in children. Immunotoxin SS1P targets the mesothelium antigen present in ovarian cancer, mesothelioma and pancreatic cancer. Phase I trials in which SS1P is given by bolus or continuous infusion are now underway. TGFa-PE38 targets cells expressing high levels of EGF receptor. A Phase I trial is being carried out at Duke in which TGFa-PE38 is infused into the tumors of patients with recurrent glioblastomas.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Division of Basic Sciences - NCI (NCI)
Type
Intramural Research (Z01)
Project #
1Z01BC010020-07
Application #
6762559
Study Section
(LMB)
Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
2002
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