Antibody-Drug Conjugates and Immunotoxins

The concept of delivering 'magic bullets' to treat diseases was first proposed by Paul Erlich in the early 1900's. The realization of this concept for the treatment of cancer occurred in the late 1990's 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 hematologicand solid malignancies. Finally, the volume highlights the promise that this technology holds for diverse types of human cancer.

Zusammenfassung
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.

Inhalt
Antibody Directed Delivery for Treatment of Cancer: Antibody Drug Conjugates and Immunotoxins.- Antibody-Drug Conjugate Development.- Components of ADC Development: Assay Methodologies and Challenges.- Clinical Pharmacology Strategies in the Development of Antibody-Drug Conjugates.- Predictive Biomarkers for Antibody-Drug Conjugates.- Factors Involved in the Design of Cytotoxic Payloads for Antibody-Drug Conjugates.- Linker Technology and Impact of Linker Design on ADC Properties.- Antibody-drug conjugates for the treatment of B-cell malignancies.- Targeting CD19 with SAR3419, an anti-CD19-Maytansinoid Conjugate for the Treatment of B Cell Malignancies.- Brentuximab Vedotin (SGN-35) for CD30 Positive Malignancies.- Trastuzumab Emtansine (T-DM1) for the Treatment of HER2-Positive Cancer.- CDX-011 (Glembatumumab Vedotin, CR011-vcMMAE).- Case Study: An Antibody-Drug Conjugate Targeting MUC16 for Ovarian Cancer.- EphA2 Immunoconjugate.- Anti-PSMA Antibody-Drug Conjugates.- Targeting CD56 (NCAM)-expressing Neoplasms with Lorvotuzumab Mertansine.- Studies on the Metabolism of Antibody-Drug Conjugates.- Design, Development and Characterization of Recombinant Immunotoxins Targeting HER2/neu.- The Preclinical and Clinical Evaluation of VB6-845: An Immunotoxin with a De-Immunized Payload for the Systemic Treatment of Solid Tumors.- Index.