Antibody-Drug Conjugates and Immunotoxins: From Pre-Clinical Development to Therapeutic Applications (Cancer Drug Discovery and Development Book 0)

This volume gathers the leading research on antibody-drug conjugates and immunotoxins. Following a rigorous overview, the volume delves into focused sections on all aspects of ADCs and ITs from clinical development through to targeted therapeutic applications and the latest technologies. Front Matter....Pages i-ix Front Matter....Pages 1-1 Antibody Directed Delivery for Treatment of Cancer: Antibody Drug Conjugates and Immunotoxins....Pages 3-22 Antibody–Drug Conjugate Development....Pages 23-38 Front Matter....Pages 39-39 Assay Methodologies and Challenges....Pages 41-56 Clinical Pharmacology Strategies in the Development of Antibody–Drug Conjugates....Pages 57-75 Predictive Biomarkers for Antibody–Drug Conjugates....Pages 77-90 Front Matter....Pages 91-91 Factors Involved in the Design of Cytotoxic Payloads for Antibody–Drug Conjugates....Pages 93-115 Linker Technology and Impact of Linker Design on ADC Properties....Pages 117-135 Front Matter....Pages 137-137 Antibody–Drug Conjugates for the Treatment of B-Cell Malignancies....Pages 139-147 Targeting CD19 with SAR3419, an anti-CD19-Maytansinoid Conjugate for the Treatment of B Cell Malignancies....Pages 149-160 Brentuximab Vedotin (SGN-35) for CD30-Positive Malignancies....Pages 161-175 Front Matter....Pages 177-177 Trastuzumab Emtansine (T-DM1) for the Treatment of HER2-Positive Cancer with a Focus on Breast Cancer....Pages 179-210 CDX-011 (Glembatumumab Vedotin, CR011-vcMMAE)....Pages 211-220 Case Study: An Antibody–Drug Conjugate Targeting MUC16 for Ovarian Cancer....Pages 221-239 EphA2 Immunoconjugate....Pages 241-253 Anti-PSMA Antibody-Drug Conjugates and Immunotoxins....Pages 255-272 Targeting CD56 (NCAM)-Expressing Neoplasms with Lorvotuzumab Mertansine....Pages 273-293 Front Matter....Pages 295-295 Studies on the Metabolism of Antibody–Drug Conjugates....Pages 297-316 Front Matter....Pages 317-317 Design, Development, and Characterization of Recombinant Immunotoxins Targeting HER2/neu....Pages 319-348 The Preclinical and Clinical Evaluation of VB6-845: An Immunotoxin with a De-Immunized Payload for the Systemic Treatment of Solid Tumors....Pages 349-367 Back Matter....Pages 369-375 The concept of delivering 'magic bullets to treat diseases was first proposed by Paul Erlich in the early 1900s. The realization of this concept for the treatment of cancer occurred in the late 1990s with the approval of monoclonal antibody therapies. The use of monoclonal antibodies conjugated (linked) to potent cytotoxic agents (antibody-drug conjugates, ADCs) for specifically delivering cytotoxics to cancer cells was an obvious extension of antibody-based therapy. ADCs have been under intense investigation for several decades; progress, however, has been limited due to toxicity or lack of improved efficacy compared to unconjugated cytotoxics. More recently, linker technology and target selection have advanced such that several ADCs and immunotoxins are undergoing clinical testing or are approved for use. This important volume gives the latest and most comprehensive information on the topic, describing different types of ADCs and immunotoxins for both hematologic and solid malignancies. Finally, the volume highlights the promise that this technology holds for diverse types of human cancer