We’ve come a long way since Robert Hooke coined the term “cell” while observing organisms beneath a handcrafted microscope. Advancements in technology have enabled us to view the inner workings of the cell. Innovative regents have left their mark, enabling scientists unprecedented discovery. The groundbreaking invention of recombinant antibodies has taken research a step further, becoming important tools for biomedical research and are increasingly being used as clinical diagnostic and therapeutic reagents.
View More: Recombinant Rabbit Monoclonals Antibodies
How did we get here?
The path toward recombinant antibodies began with Paul Ehrlich in 1900 when he described how side-chain receptors on cells bind to a given pathogen, the mechanisms of how antibodies neutralize toxins, and induce bacterial lysis with the help of complement (1). Ehrlich was the first to propose a model for an antibody molecule in which the antibody was branched and consisted of multiple sites for binding to foreign material, known as antigen, and for the activation of the complement pathway (1).
As we proceed forward to 1948, Astrid Fagraeus described how plasma B cells are involved in antibody generation (2). David Talmage and Frank Burnet built upon Fagraeus’ research with when their clonal selection theory extended the idea that each antibody-producing cell makes antibodies of only one specificity, predicting these cells proliferate in response to the detection of antigens, cloning and thus selectively increasing antibody abundance; hence, clonal selection (3). In 1959, Rodney Porter published a report in which he used the enzyme papain to cleave the antibody molecule into three pieces of about 50,000 Da, corresponding to the two Fab (antigen-binding) and constant Fc (crystallizable) fragments. In the same year, Edelman showed that reduction of the disulfide bonds of antibodies in the presence of denaturing agents led to dissociation of the molecule into smaller pieces, now known to be the light (L) and heavy (H) chains (4). The monumental invention of monoclonals by Georges Köhler and César Milstein followed in 1975 (5).
The 1990s were dominated by the development of chimeric antibodies with human constant immunoglobulin regions and mouse variable regions to prohibit HAMA responses in patients (6). Which brings us to today, recombinant antibodies are important tools for biomedical research and are increasingly being used as clinical diagnostic and therapeutic reagents.
References:
1.) Kaufmann, Stefan HE. "Immunology's foundation: the 100-year anniversary of the Nobel Prize to Paul Ehrlich and Elie Metchnikoff." Nature immunology 9.7 (2008): 705-712.
2.) Fagraeus, Astrid. "Antibody Production in relation to the Development of Plasma Cells. In vivo and in vitro Experiments." Acta Medica Scandinavica 130.Suppl. 204 (1948).
3.) Burnet, F. M. The Clonal Selection Theory of Acquired Immunity (Cambridge University Press, Cambridge, UK, 1959)
4.) Ribatti, Domenico. "Edelman's view on the discovery of antibodies." Immunology letters 164.2 (2015): 72-75.
5.) Köhler, Georges, and Cesar Milstein. "Continuous cultures of fused cells secreting antibody of predefined specificity." nature 256.5517 (1975): 495-497.
6.) Kunert, Renate, and David Reinhart. "Advances in recombinant antibody manufacturing." Applied microbiology and biotechnology 100.8 (2016): 3451-3461.