Regeneron’s COVID-19 Treatment Doesn’t Use Human Fetal Cells
I’ve seen a few memes floating around using the inflammatory language of abortion to inflame certain religious elements. Trying to demonize what may well be a life saving medication with such rhetoric isn’t wise, especially when it isn’t true. This is the kind of emotional tactic anti-science/medicine people use, so I thought I’d set the record straight by speaking to the rather cool science Regeneron actually used to create their monoclonal antibody treatment.
Just to be clear, Regeneron has stated that no human stem cells, embryonic or otherwise, are used to make this product.
“This particular discovery program (REGN-COV2) did not involve human stem cells or ESCs.”
Now to the science. I will admit some of the details are a little out of my grasp, but the work is fascinating.
Regeneron came up with the cocktail by using genetically engineered mice:
“To develop REGN-COV2, Regeneron scientists evaluated thousands of fully-human antibodies produced by the company’s VelocImmune® mice, which have been genetically modified to have a human immune system, as well as antibodies identified from humans who have recovered from COVID-19.”
Here is some of the genetic engineering it took to make the mice. This is where it gets a bit out of my depth.
“As described in the companion paper (39), the human IgH and kappa light chain (IgK) variable sequences were introduced via stepwise insertion of 13 large compound bacterial artificial chromosome (BAC) targeting vectors (LC-BACvecs) bearing overlapping fragments of the human germ-line variable loci into mouse ES cells. At several points, ES cells bearing a portion of the human IgH or IgK variable repertoire were microinjected and the resulting mice bred to create multiple versions of VelocImmune mice with progressively larger fractions of the human germ-line Ig repertoires (Fig. 1). Because the genomic regions encoding the mouse VH, DH, and JH segments, and VK and JK segments, have been completely replaced, VelocImmune mice generate only antibodies with human variable regions linked to mouse constant regions. The mouse Ig lambda loci remain intact in all versions of the VelocImmune mice described here and serve as a comparator for efficiency of expression of the various VelocImmune kappa loci (see below).”
More on manipulating mouse embryonic stem cells:
“Regeneron has created a more efficient platform for the discovery of antibody therapeutics through the use of VelociGene technology, a proprietary, high-throughput process using automated systems to make virtually any genetic modification in mouse Embryonic Stem (ES) cells. The speed and precision of VelociGene technology permits the direct exchange of large (100–200 kilobase) genomic DNA sequences in situ, allowing the manipulation of complex genomic loci in murine ES cells.”
Of course, producing monoclonal antibodies in mice is great for small scale operations. But once you know what antibodies you want in your cocktail you need to manufacture them in useful quantities for clinical development and commercial production. For that Regeneron turned to one of the workhorses of the biotech world, Chinese Hamster Ovary (CHO) cells. They genetically engineered CHO cells to produce the protein (monoclonal antibodies) they wanted.
“The companies then put the genes in Chinese hamster ovary cells to bulk manufacture the antibodies, which were given to the COVID-19 patients as infusions.”
There you have it. From discovery to production, no human cells were used, although the innovative use of genetic engineering was pretty cool. Regeneron supports human stem cell research, as do I. Here is their position statement, but for making this product those types of cells were not used.
In anticipation of any conflict of interest questions, no, I’ve never worked for Regeneron. 😉
References:
Trump’s Regeneron Monoclonal Antibody Treatment Wasn’t Made with Human Fetal Stem Cells
https://heavy.com/news/regeneron-monoclonal-antibodies-not-from-human-fetal-embryo-stem-cells/
REGENERON’S REGN-COV2 ANTIBODY COCKTAIL REDUCED VIRAL LEVELS AND IMPROVED SYMPTOMS IN NON-HOSPITALIZED COVID-19 PATIENTS
Human Antibody Discovery: VelocImmune A novel platform
https://www.pharmafocusasia.com/clinical-trials/human-antibody-discovery
Mice with megabase humanization of their immunoglobulin genes generate antibodies as efficiently as normal mice
https://www.pnas.org/content/111/14/5153
Provocative results’ boost hopes of antibody treatment for COVID-19
https://www.sciencemag.org/news/2020/09/provocative-results-boost-hopes-antibody-treatment-covid-19
Regeneron Position Statement on Stem Cell Research
https://www.regeneron.com/sites/default/files/Regeneron-Position-Stem-Cell-Research.pdf
