caa a22 4500 397562780 CHVBK 20180308164820.0 cr unu---uuuuu 161202e19960221xx s 000 0 eng 10.1093/jnci/88.3-4.153 doi (NATIONALLICENCE)oxford-10.1093/jnci/88.3-4.153 Antibody-Enzyme Conjugates for Cancer Therapy [Elektronische Daten] [Roger G. Melton, Roger F. Sherwood] The use of antibody-enzyme conjugates directed at tumor-associated antigens to achieve site-specific activation of prodrugs to potent cytotoxic species, termed "antibody-directed enzyme prodrug therapy” (ADEPT), has attracted considerable interest since the concept was first described in 1987. Prodrug forms of both clinically used anticancer agents and novel cytotoxic compounds have been developed to take advantage of potential prodrug-generating technology employing a variety of enzymes with widely differing substrate specificities. A particular advantage of the ADEPT approach is that it may allow the use of extremely potent agents such as nitrogen mustards and palytoxin, which are too toxic to be readily used in conventional chemotherapy. Preliminary studies using an antibody-enzyme conjugate constructed with a bacterial enzyme and a murine monoclonal antibody not only have established the value of the ADEPT technique, but also have highlighted the potential problem of immunogenicity of proteins of nonhuman origin. This problem has been tackled in the first instance by the use of immunosuppressive agents, but long-term solutions are being investigated in the development of second-generation ADEPT systems, including the development of human antibody-human enzyme fusion proteins and catalytic antibodies. Such improvements, coupled with further refinement of the prodrug-drug element of the system and the wide variety of antibody-enzyme-drug combinations available, should mean that ADEPT-based approaches will form an important element of the search for the anticancer drugs of the future. [J Natl Cancer Inst 1996;88:153-65] © Oxford University Press REVIEW nationallicence Melton Roger G. Centre for Applied Microbiology and Research Porton Down, Salisbury, U.K. aut Sherwood Roger F. Duramed Europe Ltd., Magdalen Centre Oxford Science Park, Oxford, U.K. aut JNCI: Journal of the National Cancer Institute Oxford University Press 88/3-4(1996-02-21), 153-165 0027-8874 88:3-4<153 1996 88 jnci https://doi.org/10.1093/jnci/88.3-4.153 text/html Onlinezugriff via DOI 1 review-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/jnci/88.3-4.153 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Melton Roger G. Centre for Applied Microbiology and Research Porton Down, Salisbury, U.K aut NATIONALLICENCE 700 1- Sherwood Roger F. Duramed Europe Ltd., Magdalen Centre Oxford Science Park, Oxford, U.K aut NATIONALLICENCE 773 0- JNCI: Journal of the National Cancer Institute Oxford University Press 88/3-4(1996-02-21), 153-165 0027-8874 88:3-4<153 1996 88 jnci Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford