The firm’s antibody technology platforms encompass two approaches: molecule-based antibody screening (MBAS) and CBAS. MBAS involves the conventional phagemid display of human antibody libraries covering IgM, IgD, and IgG repertoires as well as a newer technology called AffiScreeN™, which is a high-throughput screening technology for validated targets.
AffiScreeN allows the direct isolation of human antibodies from libraries made from the samples of patients or vaccines without the need for preselection on the basis of their binding characteristics. It uses automation by robot filter screening, which leads to faster output than conventional antibody screening methods, says Dr. Das.
The combination of the conventional phagemid screening and the AffiScreeN gives an improved selection of new antibodies for known or unknown targets from pure proteins, peptides, cell membranes, or cell lysates, and provides Affitech with a competitive edge in discovering antibodies against various targets, according to the company.
CBAS is an in vitro reverse-screening approach starting with cells and tissues for the discovery of both antibodies and their targets from disease-specific cells, which generates results faster than by more traditional genomic- or proteomic-based systems. In the latter, going from target identification through antibody identification and validation and into clinical development would take, typically, four to five years. The CBAS approach, starting from cells and including target and antibody identification and validation, will take two to three years to reach clinical development, reports Dr. Das.
In CBAS, the use of intact disease cells for antibody and target discovery enables the generation of antibodies having high affinity for targets in their normal membrane-bound configuration. Subtractive screening leads to the identification of cell-type/disease-specific cell-surface antigens. CBAS, therefore, offers obvious advantages at a time when the discovery of novel targets is one of the most difficult aspects of early-stage antibody research.
Affitech has applied CBAS to many human cancer cell types including breast, bladder, pancreatic, colon, lung, and prostate. The resulting antibodies tend to show a high level of antibody-mediated cancer-cell killing activity alone and also when tested as an immunotoxin. They also demonstrate excellent immunohistochemistry data on nanomolar affinity, Dr. Das claims.
Both the MBAS and CBAS systems have significant quality, time, safety, and cost advantages over other antibody discovery technologies, reports Affitech. Currently, the company has used these approaches to generate three antibodies that are in preclinical R&D for cancer and has several more in the pipeline coming from their in-house research as well as various collaborations.