Cytotoxic Payloads for Antibody – Drug Conjugates
CHAPTER 2: Design Factors Important for Antibody–Drug Conjugate (ADC) Payloads
Published:11 Jul 2019
John M. Lambert, 2019. "Design Factors Important for Antibody–Drug Conjugate (ADC) Payloads", Cytotoxic Payloads for Antibody – Drug Conjugates, David E Thurston, Paul J M Jackson
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The ultimate goal of cancer therapy is to eradicate all tumour cells. The magnitude of the challenge is illustrated in Figure 2.1A. At diagnosis, the volume of a patient's cancer may be in the range of 1012 cells in cases of extensive disease. Achieving this degree of tumour cell kill with cytotoxic chemotherapy is extraordinarily difficult at tolerated doses.1,2 Combination chemotherapy, first developed by Emil “Tom” Frei and others using agents with non-overlapping toxicity profiles,1,2 was able to increase the period of complete remission (i.e., to a cancer volume below the level of detection; perhaps 1010 cancer cells), and has become the mainstay of cancer treatment.2 However, long-term clinical benefit is rarely achieved by combination chemotherapy in adult patients with disseminated or metastatic disease.