Mechanisms of Action and Limitations of Monoclonal Antibodies and Single Chain Fragment Variable (scFv) in the Treatment of Cancer

Abstract

Monoclonal antibodies are among the most effective tools for detecting tumor-associated antigens. The U.S. Food and Drug Administration (FDA) has approved more than 36 therapeutic antibodies for developing novel alternative therapies that have significant success rates in fighting cancer. However, some functional limitations have been described, such as their access to solid tumors and low interaction with the immune system. Single-chain variable fragments (scFv) are versatile and easy to produce, and being an attractive tool for use in immunotherapy models. The small size of scFv can be advantageous for treatment due to its short half-life and other characteristics related to the structural and functional aspects of the antibodies. Therefore, the main objective of this review was to describe the current situation regarding the mechanisms of action, applications, and limitations of monoclonal antibodies and scFv in the treatment of cancer.

CD19/CD20 dual-targeted chimeric antigen receptor-engineered natural killer cells exhibit improved cytotoxicity against acute lymphoblastic leukemia

“…Hence, various linker molecules, predominantly based on Gly and Ser repeat peptides such as (Gly 4 Ser) 3 , consists of three repetitions Gly-Gly-Gly-Gly-Ser [ 41 ], have successfully designed scFvs. These residues provide the linker with flexibility to minimize interference with the folding of attached protein domains [ 42 ]. Moreover, the optimal linker length, usually 15–20 amino acids, prevents aggregation, as excessively short linkers can induce non-antigen-dependent CAR aggregation, leading to tonic signaling, CAR-T depletion, and incapacitation [ 43 ].…”

“…The CAR molecular structure employed in this study is of the second-generation type, with optimized linkers connecting FMC63 scFv (anti-CD19) and lEU16 scFv (anti-CD20) to the CD8α transmembrane domain, 4-1BB costimulatory domain, and CD3ζ signal transduction domain through the hinge region. Notably, CAR molecules featuring 4-1BB as the signal domain exhibited superior in vivo proliferation and killing capabilities compared to those with CD28 [ 42 ]. The inclusion of CD3ζ, a signaling component of T cells, enhances CAR-T cell signaling function.…”

Recent Advances in the Development of Monoclonal Antibodies and Next-Generation Antibodies

“…Currently, scFvs remain the most popular Ab fragment in both diagnostic and therapeutic research. Stable minimum Ag binding fragments, scFvs can be expressed on a large scale in both eukaryotic and prokaryotic systems and are easily engineered ( 103 ). bsAbs with two binding sites aimed at two distinct Ags or two distinct epitopes on a single Ag are considered more sophisticated and can outperform mAbs.…”

Production of Monoclonal Antibodies for Therapeutic Purposes: Applications, Techniques, and Improvement

“…Some mAbs can also internalize the antibody-antigen complex, removing the receptor and ligand from contact, and blocking their signaling or biological activity. Conjugated mAbs combine the benefits of mAbs with the ability to transport and release specific therapeutic agents [43,44], such as cytotoxic molecules or drugs, to exert their effects within target cells [45].…”