Abstract

Phase I trials in solid tumors with immunotoxin LMB-9 are being carried out by Dr. Lee Pai-Scherf and are described in detail in her report. LMB-9 is a stable recombinant immunotoxin produced by genetic engineering. Dr. Robert Kreitman has completed a Phase I trail on leukemias and lymphomas with LMB-2 [anti-Tac(Fv)-PE38] that targets the alpha subunit of the IL2 receptor. In this trial, several striking responses were observed. A Phase II trial is being planned. A clinical lot of an immunotoxin (BL22) that targets CD22 present on B-cell malignancies has been produced, and a Phase I trial opened by Dr. Kreitman. Dr. Robert Rand at the John Wayne Cancer Center, in collaboration with Raj Puri, FDA, Robert Kreitman, and Ira Pastan, has carried out a Phase I study in glioblastomas in which IL4-PE38KDEL is slowly perfused into the tumor site. In this chimeric toxin, the carboxyl terminus is mutated to KDEL to increase cytotoxic activity. The trial has recently been expanded to other centers by Neurocrine Bioscience, a company that has licensed the recombinant toxin and is supervising the expanded trials. - breast cancer, colorectal cancer, immunotherapy, immunotoxins, Leukemia, Lymphoma, monoclonal antibodies, - Human Subjects

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Intramural Research (Z01)
Project #
1Z01BC010020-04
Application #
6289294
Study Section
Special Emphasis Panel (LMB)
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
National Cancer Institute Division of 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
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
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
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