In situ production of therapeutic monoclonal antibodies

Todd J Suscovich1, Galit Alter

  • 1Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.

Expert Review of Vaccines
|January 13, 2015
PubMed

The use of antibodies as a treatment for disease has it origins in experiments performed in the 1890s, and since these initial experiments, monoclonal antibodies (mAbs) have become one of the fastest growing therapeutic classes for the treatment of cancer, autoimmune disease, and infectious diseases. However, treatment with therapeutic mAbs often requires high doses given via long infusions or multiple injections, which, coupled with the prohibitively high cost associated with the production of clinical-grade proteins and the transient serum half-lives that necessitate multiple administrations to gain therapeutic benefits, makes large-scale treatment of patients, especially patients in the developing world, difficult. Due to their low-cost and rapid scalability, nucleic acid-based approaches to deliver antibody gene sequences for in situ mAb production have gained substantial traction. In this review, we discuss new approaches to produce therapeutic mAbs in situ to overcome the need for the passive infusion of purified protein.

Related Concept Videos

Hybridoma Technology01:31

Hybridoma Technology

Hybridoma technology is used for the large-scale production of monoclonal antibodies. Monoclonal antibodies bind to only a single antigenic determinant or epitope. Such antibodies are used in research, diagnostics, and disease therapy. The hybridoma technology established in 1975 by Georges Köhler and Cesar Milstein was awarded the Nobel Prize in Medicine in 1984 for revolutionizing research and therapy.
Hybridoma Selection
Commonly used fusion techniques — electroporation,...
18.7K
Production of Pharmaceuticals01:30

Production of Pharmaceuticals

Industrial insulin production uses genetically engineered E. coli expressing a proinsulin gene controlled by a tryptophan promoter and containing a methionine linker for later cleavage. The cells also carry ampicillin resistance for selective growth. Seed cultures are stored at −80 °C and production begins by thawing a small amount to inoculate starter cultures, which are progressively scaled to a 50,000-L bioreactor. In the bioreactor, E. coli grow in nutrient-rich media under...
81
Upstream Processing01:27

Upstream Processing

Upstream processing represents a critical phase in biomanufacturing, wherein biological systems such as microorganisms, mammalian cells, or insect cells are cultivated to produce therapeutic proteins, vaccines, enzymes, or other biologically derived products. This phase encompasses all steps from the selection and genetic manipulation of the production organism to the cultivation of cells in bioreactors under tightly controlled environmental conditions.Host Selection and Genetic OptimizationThe...
92