科研之友
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摘要
The development of recombinant immunotoxins as an alternative to conventional chemotherapy is promising, especially for the treatment of hematological malignancies. Protein toxins, such as Pseudomonas exotoxin (PE), are extremely potent and have significant systemic toxicity without targeting. When coupled to a CD22-targeted monoclonal antibody, the cytotoxicity of PE can be directed to the malignant CD22-positive B cells of leukemias and lymphomas. Moxetumomab pasudotox is a promising new therapy with significant activity in hairy cell leukemia (HCL) and acute lymphoblastic leukemia (ALL). Major toxicities have included elevated aminotransferases and hemolytic uremic syndrome. Additionally, many patients developed neutralizing antibodies, resulting in premature termination of treatment. Phase I/II trials in patients with relapsed/refractory HCL and ALL have generated encouraging results, with overall response rates of 86% and 30%, respectively Early-phase trials are ongoing in patients with CLL and non-Hodgkin's lymphoma. Removal of B- and T-cell epitopes from PE has yielded analogues of moxetumomab pasudotox with superior activity, reduced nonspecific toxicity and reduced immunogenicity in preclinical models.
- 出版日期2012-8
