When binding is enough: nonactivating antibody formats

Most therapeutic antibodies currently used in the clinic are based on the human IgG1 format, which is a bivalent molecule that efficiently interacts with the immune system's effector functions. In clinical applications where binding to the target alone is sufficient for therapeutic efficacy; however, engagement of the immune system is not required and may even cause unwanted side-effects. Likewise, bivalent binding to the target may negatively influence the therapeutic efficacy of an antibody. Here we discuss the state of the art for antibody-based therapeutics, designed to be nonactivating (i.e. do not engage the innate immune system's effector functions), in both monovalent and bivalent formats.