Human hybridoma cell lines that produce functional human monoclonal antibodies

This technology is a method for making human hybridoma fusion partner cell lines that are capable of producing fully human monoclonal antibodies for targeted treatment of cancer and other diseases.

Unmet Need: Human hybridoma cell line for fast and efficient production of fully human antibodies

The discovery that monoclonal antibodies (mAbs) could be produced using mouse hybridomas rapidly accelerated the field of experimental immunology, as specific antibodies could be rapidly and reliably produced. However, the application of xenogenic mAbs for human in vivo diagnostics and therapy often carries undesirable effects such as a human anti-mouse immunoglobulin response. While efforts have been made to produce fully human mAbs, progress has been hampered by the absence of human myelomas suitable for use as fusion partners that are stable and exhibit high antibody production. As such, there is a need for fully human, natural fusion partner cells lines that in hybridomas that stably produce fully humanized antibodies.

The Technology: Karyochi-based human hybridomas for fast and efficient production of fully human antibodies

This technology describes a method for making human Karyochi cells that may be fused to human antibody-secreting lymphocytes to create human hybridomas. Human Karyochi cells are made by isolating a donor nucleus from either a normal or malignant B-lymphocyte, and transferring the donor nucleus into the cytoplasm of a recipient cell from a second T- or B-lymphoid cell line. With time the nuclei synchronize and fuse to form the chimeric Karyochi fusion partner cell line. Unlike existing production methods, Karyochi-based human hybridomas produce fully human mAbs for treatment of cancer, production of vaccines, and diagnostic tests without costly and time-consuming humanization steps. Additionally, the antibodies secreted by Karyochi-based human hybridomas are full-size immunoglobulins with naturally-assembled heavy and light chains as well as both antigen-binding and effector domains, whereas humanized antibodies often lack the effector domain.

The increased mAb production efficiency of Karyochi-based human hybridomas has been established through comparison both to other human-based cell lines and to non-human hybridoma lines.

Applications:

• Generation of fully human mAbs in vivo or in vitro
• Human mAbs can be used for diagnosis and treatment of cancer and other diseases
• Karyochi-based hybridoma technology for vaccine production
• Production of patient- and disease-specific antibodies

Advantages:

• Method can evolve fully human antibodies as a result of natural immune response
• Produces fully human antibodies to desired antigens in vitro
• Efficient production of large quantities of human antibodies
• Human antibodies are better tolerated by patients’ immune systems and therefore more effective
• Direct production of human antibodies avoids costly and time-consuming humanization steps

Lead Inventor:

Ilya Trakht, Ph.D.

Patent Information:

Patent Issued (US 8,859,278)

Related Publications:

• Kalantarov GF, Rudchenko SA, Lobel L, Trakht I. “Development of a fusion partner cell line for efficient production of human monoclonal antibodies from peripheral blood lymphocytes” Hum Antibodies. 2002 Nov;11(3): 85-96.

Tech Ventures Reference:

• IR 1820

• Licensing Contact: Jerry Kokoshka