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

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

This quantity gathers the prime learn on antibody-drug conjugates and immunotoxins. Following a rigorous evaluation, the amount delves into centred sections on all facets of ADCs and ITs from medical improvement via to specified healing purposes and the newest technologies.

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

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For the purpose of this discussion, the term conjugate refers to the ADC. Nonclinical approaches described in this section are based on the experience gained with ADCs currently in development, but other approaches not described below may also be applicable. As for any pharmaceutical agent, nonclinical evaluations to support first-in-human studies are conducted to identify the pharmacologic properties of the product, to understand the toxicity profile of the product and guide adequate monitoring in patients, and to establish a safe-starting dose in humans.

Protein Eng Des Sel 19(7):299–307 25. Imanishi T, Makela O (1974) Inheritance of antibody specificity. I. Anti-(4-hydroxy-3nitrophenyl)acetyl of the mouse primary response. J Exp Med 140(6):1498–1510 26. Imanishi T, Makela O (1974) Inheritance of fine-specificity in mouse anti-hapten antibodies. Ann Immunol (Paris) 125C(1–2):199–200 27. Bothwell AL et al (1981) Heavy chain variable region contribution to the NPb family of antibodies: somatic mutation evident in a gamma 2a variable region. Cell 24(3):625–637 28.

Measurement of these three components is important because the intact conjugate plays the role of proving the concept that the entity not only is in fact acting as a conjugate but also is stable in circulation; plasma levels of total antibody and unbound SMD give information as to what is happening to the conjugate once in circulation. For example, high levels of free SMD would raise both efficacy and safety concerns because high SMD concentrations would indicate less drug available at the target site for exerting efficacy, and a higher systemic exposures could lead to greater toxicity.

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