Today,
monoclonal antibodies (mAbs) are a widespread and necessary tool for biomedical science. In the hematological
cancer field, since
rituximab became the first mAb approved by the Food and Drug Administration for the treatment of B-cell
malignancies, a number of effective mAbs targeting lineage-specific
antigens (LSAs) have been successfully developed. Non-LSAs (NLSAs) are molecules that are not restricted to specific leukocyte subsets or tissues but play relevant pathogenic roles in
blood cancers including the development, proliferation, survival, and refractoriness to
therapy of
tumor cells. In consequence, efforts to target NLSAs have resulted in a plethora of mAbs-marketed or in development-to achieve different goals like neutralizing oncogenic pathways, blocking
tumor-related chemotactic pathways, mobilizing malignant cells from tumor microenvironment to peripheral blood, modulating immune-checkpoints, or delivering cytotoxic drugs into
tumor cells. Here, we extensively review several novel mAbs directed against NLSAs undergoing clinical evaluation for treating
hematological malignancies. The review focuses on the structure of these
antibodies, proposed mechanisms of action, efficacy and safety profile in clinical studies, and their potential applications in the treatment of
hematological malignancies.