Cancer Therapeutic Antibodies

Abstract

Cancer consistently ranks among the top causes of death worldwide. Traditional therapies include surgery, chemotherapy, and radiation. However, many patients either do not respond to or develop specific treatment resistance. Given the advent of genome, transcriptome, and proteome technologies, personalized medicine has gained tremendous recognition as a therapeutic field. Antibodies are Y-shaped proteins produced by activated B immune cells, featuring two substrate recognition sites. They identify and bind to invading pathogens, such as bacteria, viruses, and toxins to help prevent and eliminate infections. The concept and potential of therapeutic monoclonal antibodies (mAbs) in cancer was put forth by Paul Ehrlich over a century ago. A breakthrough by Köhler and Milstein (Cambridge, 1975) followed the development of hybridoma technology, allowing mass production of specific antigen-induced mAbs. MAbs exert their effect through various mechanisms to combat malignancies. Depending on their design, mAbs bind to specific cognate cell-surface receptors to modulate (insert = cell) growth, apoptosis, and immune recognition. MAbs targeting various cancer types have received clinical approval. For instance, rituximab binds CD20 expressed on B cell non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL), leading to immune-mediated target cell destruction. A class of mAbs known as immune checkpoint inhibitors (ICIs), activate the body's natural immune response against tumor cells by blocking their suppression. Notable ICI include pembrolizumab and nivolumab, which specifically target the programmed cell death receptor-1 (PD-1). Unlike traditional therapies which often cause damage to healthy cells, mAbs are intrinsically target-specific, reducing or eliminating harmful side effects. As such, they have emerged to provide more effective and less toxic options for cancer patients.