Immunotoxins for Treating Cancer and Autoimmune Disease
Year: 2019
Type: book-chapter
Abstract: At the time nearly half of all human malignancies remain incurable, primarily due to the ineffectiveness of therapy for systemic cancer. Often, the metastatic cells that are least amenable to cytotoxic chemotherapy are composed of relatively differentiated malignant cells, which are biochemically similar to their nonmalignant cell of origin. Plants and bacteria produce protein toxins which interfere with protein synthesis in animal cells. Plant toxins, such as ricin, gelonin, pokeweed antiviral protein, and saporin inhibit protein synthesis by inactivating ribosomes, while bacterial toxins including Pseudomonas exotoxin (PE) and diphtheria toxin, inactivate elongation factor 2 (EF-2). The full-length 613 amino acid PE contains three functional domains which are necessary for cellular intoxication. Domain Ia (amino acids 1-252) is the binding domain, domain II (amino acids 253-364) is responsible for translocating the toxin to the cytosol, and domain III (amino acids 400-613) contains the ADP-ribosylating enzyme which inactivates EF-2 in the cytosol and results in cell death.
Source: Antibody Therapeutics
Authors: Robert J. Kreitman, Ira Pastan
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,822
OpenAlex ID: W2982471725