Research and development of next generation of antibody-based therapeutics

Abstract

Monoclonal antibodies (mAb) are emerging as one of the major class of therapeutic agents in the treatment of many human diseases, in particular in cancer and immunological disorders. To date, 28 mAb have been approved by the United States Food and Drug Administration for clinical applications. In addition, several hundreds of mAb are being developed clinically by many biotech and pharmaceutical companies for various disease indications. Many challenges still remain, however, and the full potential of therapeutic antibodies has yet to be realized. With the advancement of antibody engineering technologies and our further understanding of disease biology as well as antibody mechanism of action, many classes of novel antibody formats or antibody derived molecules are emerging as promising new generation therapeutics. These new antibody formats or molecules are carefully designed and engineered to acquire special features, such as improved pharmacokinetics, increased selectivity, and enhanced efficacy. These new agents may have the potential to revolutionize both our thinking and practice in the efforts to research and develop next generation antibody-based therapeutics.

Antibody-Based Immunotoxins for the Treatment of Cancer

“…It is composed from the variable domains VH and VL of the murine anti-CD25 MAb anti T-cell activation antigen (Tac), fused in a scFv form via a peptide linker (G4S) 3 , and the VL is further fused at its C-terminus to PE38 via a short connector ASGGPE [40]. CD25 is the  chain of the interleukin-2 receptor (IL-2R) [58].…”

“…Antibody-based therapeutics are of growing significance in cancer therapy, and so far 28 such drugs have been approved for cancer therapy by the US Food and Drug Administration (FDA) for marketing in the USA, with combined global revenues that exceed US $50 billion [3]. The market for therapeutic antibodies is the fastest growing sector in the pharmaceutical industry.…”

“…These are highly potent and active in very small quantities, such that killing a cell is possible even by a single molecule in the cytoplasm [9]. Another new approach in therapeutic antibody development is to bind the antibody to non-protein therapeutic payloads, such as radioactive isotopes or chemotherapeutic drugs to target cells [3]. The field of antibody drug conjugates (ADCs) in which the toxic moiety is not a protein has been reviewed recently [10,11] and will not be discussed here.…”

Function characterization of a glyco-engineered anti-EGFR monoclonal antibody cetuximab in vitro

“…Glycosylation is one of the most important post-translational protein modifications and has essential roles in therapeutic antibody function, including effector function, immunogenicity, half-life in serum and other aspects of bioactivity [3,4] . Some glycoforms of human antibodies exhibit stronger therapeutic effects than other glycoforms, and some glycoforms possess undesired properties.…”

Glycoengineered Yeast as an Alternative Monoclonal Antibody Discovery and Production Platform

“…Following marketing of the first therapeutic antibody, Muromonab-CD3 in 1986, mAbs used in the clinic have evolved over the years from entirely murine to mouse-human chimeric, and then to humanized and finally fully human antibodies in order to minimize anti-drug related immunogenicity in patients and maintain maximum potency (Li and Zhu, 2010). Several different antibody discovery technologies co-exist today in therapeutic antibody development ranging from isolating antibodies from immunized mice or engineered mice carrying human Ig-repertoire genes to flow-cytometric isolation of human antibodies from non-immune yeast display or panning a large non-immunized phage display libraries (Feldhaus et al, 2003;Vaughan et al, 1996;Weaver-Feldhaus et al, 2004).…”