Our goal is to evaluate clinical activity of rcombinant immunotoxins in patients. HA22 ia licensed to MedImmune who are sponsoring trial in B cell malignancies. A multi center phase 1 trial of HA22 (CAT-8015, moxetumomab pasudotox) in drug resistant hairy cell leukemia is completed and is now being expanded at the MTD. There have been no dose limiting toxicities and about 40% of patients have achieved a complete remission. A multi center phase 1 trial of HA22 in refectory ALL has opened and 12 patients treated. Clinical activity with 3 complete remissions has been observed. This is a collaboration with Dr. Alan Wayne of the Pediatric Oncology Branch. Fourteen patients with mesothelioma have been treated with SS1P plus chemotherapy. No dose limiting toxicity has occurred and six partial responses observed. We are now at the MTD and will treat 6 more patients this dose level. A multi-center phase 2 trial in mesothelioma combining MORAB-009 with chemotherapy has opened. Dr Hassan is PI on this trial. Trial with LMB2 in CTL and ATL are ongoing.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC010020-15
Application #
8157245
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
15
Fiscal Year
2010
Total Cost
$1,230,498
Indirect Cost
Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
Chandramohan, Vidyalakshmi; Pegram, Charles N; Piao, Hailan et al. (2017) Production and quality control assessment of a GLP-grade immunotoxin, D2C7-(scdsFv)-PE38KDEL, for a phase I/II clinical trial. Appl Microbiol Biotechnol 101:2747-2766
Hassan, Raffit; Alewine, Christine; Pastan, Ira (2016) New Life for Immunotoxin Cancer Therapy. Clin Cancer Res 22:1055-8
Hassan, Raffit; Thomas, Anish; Alewine, Christine et al. (2016) Mesothelin Immunotherapy for Cancer: Ready for Prime Time? J Clin Oncol 34:4171-4179
Bao, Xuhui; Pastan, Ira; Bigner, Darell D et al. (2016) EGFR/EGFRvIII-targeted immunotoxin therapy for the treatment of glioblastomas via convection-enhanced delivery. Receptors Clin Investig 3:
Pastan, Ira; Hassan, Raffit (2014) Discovery of mesothelin and exploiting it as a target for immunotherapy. Cancer Res 74:2907-12
Sharon, Elad; Zhang, Jingli; Hollevoet, Kevin et al. (2012) Serum mesothelin and megakaryocyte potentiating factor in pancreatic and biliary cancers. Clin Chem Lab Med 50:721-5
Kelly, Ronan J; Sharon, Elad; Pastan, Ira et al. (2012) Mesothelin-targeted agents in clinical trials and in preclinical development. Mol Cancer Ther 11:517-25
Kreitman, Robert J; Tallman, Martin S; Robak, Tadeusz et al. (2012) Phase I trial of anti-CD22 recombinant immunotoxin moxetumomab pasudotox (CAT-8015 or HA22) in patients with hairy cell leukemia. J Clin Oncol 30:1822-8
Mehta, Ankit I; Choi, Bryan D; Ajay, Divya et al. (2012) Convection enhanced delivery of macromolecules for brain tumors. Curr Drug Discov Technol 9:305-10
Mehta, Ankit I; Choi, Bryan D; Raghavan, Raghu et al. (2011) Imaging of convection enhanced delivery of toxins in humans. Toxins (Basel) 3:201-6

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