HA22 is licensed to Medimmune and been given the name Moxetumomab pasudotox (Moxe). It has been tested in patients with advanced chemo-resistant hairy cell leukemia (HCL) in adults and in acute lymphoblastic leukemia in children. The HCL phase 3 trial has met its FDA mandated efficacy endpoint and the agent and was approved by the FDA in 2018. New trials with Moxe are planned in patients in combination with Rituxan to determine if the complete response rate is increased with the goal of using combination in patients who have never been previously treated to avoid the bone marrow damaging effects of purine analog therapy. LMB-100 is an immunotoxin targeting mesothelin expressing cancers. In collaboration with Drs Hassan and Alewine, we tested in patients with mesothelioma and pancreatic cancer LMB-100 as a single agent and in combination with Abraxane, but the response rate was not increased by Abraxane. Because the development of anti-drug antibodies to agents like LMB-100 interferes with the activity of immunotoxins in humans, we have collaborated with Selecta Biosciences and shown in mice that ADA formation vs immunotoxins is prevented and immune tolerance induced by co-administration nanoparticles containing rapamycin. A clinical trial combining these 2 agents has been opened. Unexpectedly we found that patients developed side effects that were too severe to continue the trial and the trial was closed. Our next plan is to test LMB-100 with pembrolizimab in patients with mesothelioma and also to test LMB-100 with Tofacitinib in patients with pancreatic cancer. In mouse models Tofa has been found to suppress anti-drug antibody formation and to enhance killing of tumor cells by LMB-100.
| 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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