| Abstract: |
Anticancer therapy using monoclonal antibodies (mAbs) is a rapidly evolving treatment modality with major clinical impact. Their tumor selectivity enables precision, thereby minimizing side effects. Novel genetic engineering methods have produced multifunctional constructs, drug conjugates, radioimmunoconjugates, immunocytokines, immunotoxins, immunoenzymes, immunoliposomes, and bispecific immune effector cell engagers. In the last two decades, numerous clinical trials with naked and conjugated mAbs have demonstrated significant improvements in tumor response and survival for different malignancies, resulting in a rapid expansion of the antibody armamentarium worldwide. Immune checkpoint inhibitors (ICIs) and antibodies that modify the tumor microenvironment have further energized the entire field of immunotherapy. Although ICIs have dramatically changed the therapeutic landscape in melanoma and non-small cell lung cancers, they have added another dimension to the conventional approach of naked antibodies and antibody immunoconjugates. The integration of these different antibody-based approaches into the emerging fields in cellular therapy and small molecules and the revisiting of conventional chemotherapy should ultimately maximize the curative potential of these approaches. Even among antibodies, mAbs do not have overlapping mechanisms of action or toxicity profiles, allowing for further exploration of dose, schedule, and multimodality combinations, especially at the time of minimal residual disease. This chapter emphasizes the evolution of antibody therapy from seminal preclinical work to successful clinical trials that lead to drug approval. © 2020 Elsevier Inc. |
