Download Antibody-Drug Conjugates and Immunotoxins: From Pre-Clinical by Pamela A. Trail (auth.), Gail Lewis Phillips (eds.) PDF

By Pamela A. Trail (auth.), Gail Lewis Phillips (eds.)

This quantity gathers the top study on antibody-drug conjugates and immunotoxins. Following a rigorous evaluation, the quantity delves into targeted sections on all points of ADCs and ITs from medical improvement via to distinct healing functions and the newest technologies.

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Additional info for Antibody-Drug Conjugates and Immunotoxins: From Pre-Clinical Development to Therapeutic Applications

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Law CL et al (2004) Efficient elimination of B-lineage lymphomas by anti-CD20-auristatin conjugates. Clin Cancer Res 10(23):7842–7851 15. Sutherland MS et al (2006) Lysosomal trafficking and cysteine protease metabolism confer target-specific cytotoxicity by peptide-linked anti-CD30-auristatin conjugates. J Biol Chem 281(15):10540–10547 16. Alley SC et al (2008) Contribution of linker stability to the activities of anticancer immunoconjugates. Bioconjug Chem 19(3):759–765 17. Lewis Phillips GD (2008) Targeting HER2-positive breast cancer with trastuzumab-DM1, an antibody-cytotoxic drug conjugate.

The challenge for the researcher is to build upon the methods used for analyzing the parent small molecule drug and unconjugated antibody to devise new, unique assays that are appropriate for the specific conjugation process and heterogeneity of the ADC’s in question. In this respect, some methods have been more challenging than others to optimize for analyzing ADCs. 3 Assay Methodologies and Challenges 43 ADC Analytical Methods and Applications There are a variety of assay methods that have been used to analyze ADCs, many of which have recently been captured in comprehensive reviews [5, 6].

An assessment of the immune response to the conjugate may be useful in the interpretation of study results. Samples may be stored and analyzed retrospectively as needed. When the SMD is a cytotoxic agent, a class of products known to cause bone marrow suppression, immunogenicity may be reduced as doses of the conjugate are increased in animals. As toxicities of the conjugates investigated to date arise mainly from the SMD moiety, a toxicokinetic evaluation to assess the levels of conjugate and the free SMD in studies conducted with the conjugate are expected, as discussed in ICH S9.

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