Smaller size packs a stronger punch - Recent advances in small antibody fragments targeting tumour-associated carbohydrate antigens

Abstract

Attached to proteins, lipids, or forming long, complex chains, glycans represent the most versatile post-translational modification in nature and surround all human cells. Unique glycan structures are monitored by the immune system and differentiate self from non-self and healthy from malignant cells. Aberrant glycosylations, termed tumour-associated carbohydrate antigens (TACAs), are a hallmark of cancer and are correlated with all aspects of cancer biology. Therefore, TACAs represent attractive targets for monoclonal antibodies for cancer diagnosis and therapy. However, due to the thick and dense glycocalyx as well as the tumour micro-environment, conventional antibodies often suffer from restricted access and limited effectiveness in vivo . To overcome this issue, many small antibody fragments have come forth, showing similar affinity with better efficiency than their full-length counterparts. Here we review small antibody fragments against specific glycans on tumour cells and highlight their advantages over conventional antibodies.

Targeting GD2-Positive Tumor Cells by Pegylated scFv Fragment–Drug Conjugates Carrying Maytansinoids DM1 and DM4

“…In the case of GD2-positive cancers, all of which are solid tumors, antibody FDCs are of particular interest. FDCs typically penetrate into solid malignant neoplasms better, accumulate in tumors in larger amounts in less time, and are able to eliminate tumors more efficiently, due to the smaller size of antibody fragments compared to full-length IgG molecules [3,7].…”

“…Due to their smaller size, antibody fragments pass through the walls of blood vessels and diffuse into the tumor faster, and are more evenly distributed throughout it [6]. All major antibody fragment formats can be employed and are being studied in this aspect, namely minibodies, Fab fragments, diabodies, scFv fragments, and nanobodies, as well as lower-molecular-weight antigen-binding peptides [3,7,8]. From this point of view, the development of antibody fragment-drug conjugates (FDC) seems reasonable as an approach combining both aforementioned strategies to improve the poor tumor penetration of GD2-targeted drugs.…”