On-cell antibody display from hybridoma cells
Lead investigator: Scott Dessain, MD, PhD
Precision medicine refers to individualized strategies to heal a patient based on his or her genetic makeup or other molecular characteristics. While such strategies emerged initially in oncology, due to the unique genetic mutations in individual tumors, they are now becoming more prevalent in other areas as trends in molecular medicine unfold. Antibody-based therapies tailored to specific disease molecules are the main biologics being developed as precision medicine.
Human monoclonal antibodies (huMab) are desired in precision medicine, but there remains a need for methods that can enable rapid cloning of antibodies to specific antigens in patients who have run a particular clinical course (e.g., cure from cancer or other deadly disease). Further, there is a gap in the ability to retain all the human post-translational modifications of the antibody to confer the highest degree of natural immune character, potency and function. In particular, there is a technical gap in the ability to clone human antibodies against native configurations of many membrane-bound antigens, often greatly desired as therapeutic targets.
The novel technology developed at LIMR permits human hybridomas to display the antibodies they express on their cell surface, thereby enabling a new suite of useful methods to obtain antibodies against epitopes otherwise difficult or impossible to clone from patients.
Rising incidence of cancer and other chronic diseases is engendering the high demand for biologics, which is serving as the key contributing factor for the growth of the monoclonal antibodies industry. In 2015 the global monoclonal antibodies (mAbs) market accounted for US $85.4B and is expected to exhibit a growth rate of 5.7% over the 2015 – 2024 period, according to the market research firm Grand View Research.
LIMR’s technology enables rapid cloning of human antibodies that may be difficult or impossible to obtain by other methods (e.g., against membrane-bound proteins in native configuration). This technology, known as the On-Cell Monoclonal antibody display System (OCMS), provides biotechnology companies with the ability to clone the broadest array of medicinal candidates from patients with a desired clinical experience. Human antibodies encompass greater antigenic diversity and reflect the experience of the patient, for example, in overcoming an aggressive cancer (where effective cancer-fighting antibodies may be found).
The technology allows human B cell hybridomas to display on their cell surface the huMAb they express. By doing so, effective methods to quickly clone desirable huMab against any defined native antigen is possible, thus enabling rapid product development for therapeutic targets that are novel or clinically validated.
The OCMS antibody-display platform enables cloning of huMab recognizing any desired native epitope on a clinically validated therapeutic target. In particular, the technology empowers cloning of biosimilar huMab to validated targets that can be positioned quickly for clinical testing,
Stage of development
Preclinical validation of several classes of huMab cloned by the LIMR Center for Human Antibody Technology (CHAT) has been demonstrated using the OCMS platform, most recently antibodies that neutralize poliovirus or rabies virus or that bind the NMDA receptor in the brain and can be used to diagnose a potentially fatal encephalitis (brain inflammation).
Pending patent: PCT patent application has been submitted.
LIMR outlicensed the OCMS technology to OCMS Bio, Wynnewood, PA.
Puligedda RD, Sharma R, Al-Saleem FH. Kouiavskaia D, Kattala CD, Velu AB. Prendergast GC, Chumakov K and Dessain SK (2019) Capture and display of antibodies secreted by human hybridoma cells enables on-cell screening. MAbs Apr;11(3):546-58.
Puligedda RD, Kouiavskaia D, Al-Saleem FH, Kattala CD, Nabi U, Yaqoob H, Bhagavathula VS, Sharma R, Chumakov K, Dessain SK (2017) Characterization of human monoclonal antibodies that neutralize multiple poliovirus serotypes. Vaccine Oct 4;35(41):5455-62.
Levites Y, O'Nuallain B, Puligedda RD, Ondrejcak T, Adekar SP, Chen C, Cruz PE, Rosario AM, Macy S, Mably AJ, Walsh DM, Vidal R, Solomon A, Brown D, Rowan MJ, Golde TE, Dessain SK (2015) A human monoclonal IgG that binds aβ assemblies and diverse amyloids exhibits anti-amyloid activities in vitro and in vivo. J Neurosci. Apr 22;35(16):6265-76.
Institutional contact: George C. Prendergast, PhD, LIMR President and CEO, 484.476.8475, [email protected]
L2C Partners contact: Merle Gilmore, 610.662.0940, [email protected]