Immunotoxins assessments

Assess the cytotoxicity of the immunotoxin conjugate by [3H]thymidine incorporation assay. Pulse cells after 56 hby the addition of 0.5 iCi/well of [3H]thymidine and incubate for another 16 h. 

Each immunotoxin is evaluated in a series of stages. These include assessment of specificity, cytotoxicity, and serum stability selection of a relevant animal species and route of drug administration and finally safety evaluation. 

Although extensive in vitro testing is performed on each immunotoxin to assess its cytotoxicity and specificity, it is animal model studies that ultimately determine the serum half-life, serum stability, as well as the efficacy of an immunotoxin. A compilation of the in vitro and in vivo data enables a decision to be made on the potential of each immunotoxin to be an effective and safe therapeutic and to determine whether human clinical trials are warranted. 

Examination of genotoxicity of pharmaceuticals is required to assess the interaction of the drug with DNA. These studies are generally not applicable to immunotoxins. Unlike chemotherapeutics that cause cell death through DNA interaction, immunotoxins mediate cell death by preventing protein synthesis. However, immunotoxins use a linker to connect the toxin to the antibody that may need to be examined if it is an organic linker and has the ability to bind DNA (per ICH S6). The majority of immunotoxins use either a nonreducible thioether linker for intact toxins or a disulfide bond for A chains and ribosome-inactivating proteins and do not interact with DNA. 

Faguet, G.B. and Agee, J.F. (1997) The chronic lymphocytic leukemia antigen (cCLLa) as immunotherapy target assessment of LD50 and MTD of four ricin-based anti-cCLLa immunotoxins (ITs) in Balb/c mice. Leuk Lymphoma, 25, 531. 

Immune System-drug effects. 5. Immunotoxins-adverse effects. 6. Risk Assessment. 

Sung, C., et al. The spatial distribution of immunotoxins in solid tumors assessment by quantitative autoradiography. Cancer Research, 1993, 53, 2092-2099. 

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