The National Institute of Standards and Technology (NIST) just released a new peptide library that could provide greater insight into CHO cells and enable better production of therapeutic proteins. The data used in the library was gathered with help from other institutions and put into a searchable format by postdoctoral researchers working in a cooperative program between NIST and MedImmune.
Today, CHO cells are engineered using gene-editing tools to insert a gene that will enable the cells to produce a particular antibody or other valuable protein. After genetic engineering, the host cells are screened to isolate the ones that make the specific target protein. The growth conditions are optimized so that the cells will grow in large number and produce significant quantities of the therapeutic protein. In order to turn the manufactured antibodies into effective drugs, the antibodies must be isolated from the host CHO cells, separated from other impurities, and appropriately formulated for patient use. Manufacturers need to be confident that their products are not contaminated by other natural proteins that originate from the CHO cells.
The current method for checking for host cell protein contamination involves making an immunoassay, but many scientists would prefer to use a mass spectrometer for testing instead. What's been missing, however, is a resource tool to check whether detected peptides originate from host cell proteins. This new mass spectral library, which contains signatures of individual biochemical components represented by peptides, fills the void.
"It is a lot like the way they use fingerprint libraries in forensics," said NIST chemist Stephen Stein, who directs the NIST Mass Spectrometry Data Center. By keeping a record of the peptides derived from various host cell proteins in CHO cell lines, CHO researchers can see if the spectra of peptides they identify in their work match any known proteins other than cells of the desired biological drug.
Quality data is especially key to the success of the peptide library. "This library provides that more complete picture, which includes all previously measured data and provides a fast and direct readout of contaminants—unlike the immunological methods in common use," Stein added.
The CHO tool is now available to the public and adds to a growing list of peptide libraries in the NIST Mass Spectrometry Data Center.
Image: A CHO-K1 cell culture is labeled with dyes, including MitoTracker Orange, Oregon Green and Hoechst. Image courtesy of Nikon MicroscopyU.