Antibody Engineering for Pursuing a Healthier Future

Abstract

Since the development of antibody-production techniques, a number of immunoglobulins have been developed on a large scale using conventional methods. Hybridoma technology opened a new horizon in the production of antibodies against target antigens of infectious pathogens, malignant diseases including autoimmune disorders, and numerous potent toxins. However, these clinical humanized or chimeric murine antibodies have several limitations and complexities. Therefore, to overcome these difficulties, recent advances in genetic engineering techniques and phage display technique have allowed the production of highly specific recombinant antibodies. These engineered antibodies have been constructed in the hunt for novel therapeutic drugs equipped with enhanced immunoprotective abilities, such as engaging immune effector functions, effective development of fusion proteins, efficient tumor and tissue penetration, and high-affinity antibodies directed against conserved targets. Advanced antibody engineering techniques have extensive applications in the fields of immunology, biotechnology, diagnostics, and therapeutic medicines. However, there is limited knowledge regarding dynamic antibody development approaches. Therefore, this review extends beyond our understanding of conventional polyclonal and monoclonal antibodies. Furthermore, recent advances in antibody engineering techniques together with antibody fragments, display technologies, immunomodulation, and broad applications of antibodies are discussed to enhance innovative antibody production in pursuit of a healthier future for humans.

Microheterogeneity of Recombinant Antibodies: Analytics and Functional Impact

“…[2,3] Various smaller formats, including single chain variable fragments (scFv), antigen binding fragments (Fab), minibodies etc. [4] as well as antibody structures from alternative sources like camelid antibodies or immunoglobulin new antigen receptors [5] were investigated for their potential use as therapeutics. Additional efforts at engineering were made to create bispecific types of structures that can target two different antigens, [6] or even more recently, to produce antibodies that contain multiple crystallizable fragment (Fc)-domains, showing enhanced effector functions.…”

CGRP, Amylin, Immunology, and Headache Medicine

“…98 The resultant hybridoma, a collection of cells reproducing indefinitely in culture, produce clones of single antibody types, the monoclonal antibodies. 102,103 The step to producing human therapeutic mAbs with lower toxicities required changing the sourced amino acids. The mAbs often exhibit good binding affinity due to in vivo secondary immune responses.…”

“…Hybridoma technology allows robust, stable, and constant, but renewable mass production of relatively pure, predictable, and selected antibody clones with no or low variability of mAb from one production run to the next. 102 To further engineer mAbs recombinant and immunomodulatory approaches, "repertoire cloning" and "phage display" are being employed. 98,102 Potential negatives to consider include expense, ethical use of animals in research, loss of expression of the target antigen, lengthy production times, and requirement for skilled technicians with risk for human anti-mouse antibodies (HAMA).…”

“…The mAbs often exhibit good binding affinity due to in vivo secondary immune responses. 102 These recombinant methods use cloned gene segments with desired specificities, and many do not require animals, immunizing or cell culture in all instances. 102,103 The step to producing human therapeutic mAbs with lower toxicities required changing the sourced amino acids.…”

“…98,102 Potential negatives to consider include expense, ethical use of animals in research, loss of expression of the target antigen, lengthy production times, and requirement for skilled technicians with risk for human anti-mouse antibodies (HAMA). 102 Some benefits, when desired, also include smaller size fragments with exclusive renal elimination, although much shorter half-lives in minutes to hours rather than days to weeks. Hybridomas produced from rodent immunization lead to mouse-sourced amino acid mAbs.…”