Enhanced Antibody Activity Technology

ADCC enhanced antibody technology (POTELLIGENT^® Technology) and CDC enhanced antibody technology (COMPLEGENT^® Technology) that are originally developed by Kyowa Hakko Kirin, are being applied to the development of in-house therapeutic antibody and also being used as core technologies to form strategic alliances agressively to expand our therapeutic antibody business rapidly.

The ADCC (Antibody-dependent cellular cytotoxicity) mechanism is one of the human immune functions which permits white blood cells like natural killer cells and monocytes to kill other target cells such as cancer cells in the presence of antibodies.
The ADCC mechanism is one of the primary anti-tumor mechanisms of therapeutic antibodies already on the market such as Herceptin (a pharmaceutical for metastatic breast cancer) and Rituxan (a pharmaceutical for non-Hodgkin's lymphoma). The further enhancement of this mechanism is attracting global attention as a next-generation antibody engeneering technology. Such enhancement will bring with it benefits in terms of side effects thanks to its highly efficacious nature even in small doses.

JBC Online dated November 8, 2002. ; J. Biol. Chem, 10.1074/jbc.M210665200

The main feature of ADCC enhanced antibody technology POTELLIGENT^®, originally developed by Kyowa Hakko Kirin, is its ability to remarkably increase the ADCC activity by reducing the amount of the fucose in the carbohydrate structure of antibodies, thus causing the extremely effective elimination of target cells, such as cancer cells.

Though there have been some reports trying to enhance the antibody activity by focusing on other parts of the carbohydrate structure other than fucose or amino acid substitution, the enhancements by such technology have not been shown to be greater than the one by POTELLIGENT^® Technology.

The experiment using animals has confirmed that antibodies using POTELLIGENT^® technology are over a hundred times more effective against tumors than normal antibodies, and the technology has also contributed to the discovery of anti-therapeutic antibodies.

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The CDC enhanced antibody technology COMPLEGENT^® has been originally developed that enhance the efficacy of therapeutic antibodies as well as POTELLIGENT^®.

Complement dependent cytotoxicity (CDC), is one of activity of antibody where activated complement kills the target cell.
Complement is a mechanism acquired by multi-cellular organism to defend themselves against foreign organisms. Complement, activated by binding to antigen-antibody complex or pathological microorganisms, supports the functions of antibody, such as phagocytosis or lysis of foreign organisms.

Complement-Dependent Cytotoxicity (CDC) is one of the major pharmacological effects of therapeutic antibodies as well as Antibody-Dependent Cellular Cytotoxicity (ADCC).

Immunoglobulin G molecule has several isotypes which differ in biological effects. We have successfully created an antibody molecule with enhanced CDC by incorporating a part of the amino acid sequence of IgG3 into the sequence of IgG1, (Isotype Chimerism).