Technologies
The Hu-PAC™ technology
Hu-PAC™ is the acronym for human portable antibody compartment, because it involves the transfer of genetically engineered, human antibody expressing mouse preB lymphocytes from tissue culture into mice, in which these cells engage in immunizations resulting in affinity maturation of the recombinantly expressed human antibodies.
The Retrocyte Display™ technology
Retrocyte Display™ stands for retroviral preB-lymphocyte display. This technology is based on the expression of human antibody libraries in immortalized preB lymphocytes that are then efficiently screened by in vitro techniques, like fluorescence or magnetic activated cell sorting (FACS or MACS) for antigen-reactive cells.
Both technologies are part of 4-Antibody’s unique and proprietary suite of fully human antibody discovery and engineering technologies, which can be used independently but also synergistically to develop therapeutic antibody candidates against any antigen target.
Therapeutic antibodies developed by Hu-PAC™ and Retrocyte Display™ are fully human, thereby minimizing the risk that they will be immunogenic when administrated into patients. For more information, please see the overview of therapeutic antibodies.
The Hu-PAC™ and Retrocyte Display™ advantages
4-Antibody’s Hu-PAC™ and Retrocyte Display™ technologies offer a number of advantages for developing therapeutic antibodies:
- Freedom to operate for the development of human antibodies against any target. Hu-PAC™ and Retrocyte Display™ technologies are unrestricted by patent or licensing issues and can be used to create fully human antibodies against any target. This contrasts with the exclusive licensing of clinically validated targets for current gold-standard technologies (phage display and transgenic mouse technologies), which thereby limits the opportunity to use these gold standard methods to develop fully human antibodies against most major validated targets
- High specificity, high affinity antibodies. Antibodies produced using Hu-PAC™ and Retrocyte Display™ technologies exhibit high affinity for the target antigen, as any antibody can be optimized in vivo by Hu-PAC™ using the natural somatic hypermutation and affinity maturation process induced during natural T cell dependent immune responses in the mouse’s immune system. Affinity maturation of antibodies is a natural process of the immune system during which B cells, expressing higher affine antibody mutants, are selectively enriched, which eventually results in the production of highest affine antibodies at the end of an immune reaction.
- High quality of developed antibodies. All antibodies developed by Hu-PAC™ and Retrocyte Display™ are expressed in B lymphocte lineage cells throughout the discovery process, which are the cells naturally producing antibodies in the immune system. Therefore, all necessary co-factors (chaperones, glycosylation enzymes, etc.), that ensure proper processing and expression of natural antibodies, are present throughout the discovery process at all times. This ensures strong selection for antibodies that exhibit natural structural and functional properties, e.g. proper protein folding, antibody heavy-light chain assembly, glycosylation and disulphide bridge formation, which are not always present in non-lymphocyte, lower eukaryotic or prokaryotic expression systems. Therefore, antibodies derived from Hu-PAC™ and Retrocyte Display™ technologies will be stable, manufacturable, and most compatible with further downstream clinical development and manufacturing processes.
- Non-immunogenic. Therapeutic antibodies that are fully human and produced by lymphocytes (as opposed to expression by bacteria/phage and by general genetic engineering) minimize the risk that they will be immunogenic when systemically applied to patients.
- Maximised efficiency and flexibility. The Hu-PAC™ and Retrocyte Display™ platforms can be combined with any antibody library source, either libraries from patients, libraries from any B cell source, semi-synthetic libraries, or antibody libraries resulting from initial screens using other technology platforms, like phage display of transgenic mouse technologies. This offers unparalleled flexibility in tailoring or customizing the antibody discovery process depending on the requirements of the project or the needs of a customer. Any antibody library can be used efficiently to select out optimized antibodies in vivo by Hu-PAC™, and/or to screen any antibody library in vitro for antigen reactivity by Retrocyte Display™ at rates of dozen millions of antibody clones per day. The flexibility of both technologies and the possibility to combine both in vivo and and in vitro technologies in a synergistic way, offers unprecedented efficiency and success-rates in finding antibody drug candidates to any target category.
- Creation of unique antibodies. The combination of in vitro library screening by Retrocyte Display™ and in vivo affinity maturation by Hu-PAC™ enables the development of natural antibodies that would not be possible using either phage display or transgenic animal production alone. Retrocyte Display™ further allows antibody heavy and light chain shuffling, thereby creating unusual antibody specificities that normally cannot be found in normal immune repertoires.