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R&D(Research and Development)

Therapeutic Antibody Projects

Recently, the MBL group has been focusing on the development of therapeutic antibodies. Currently, MBL is making progress in the development of therapeutic antibodies targeting cancers, infectious diseases, and inflammatory diseases. Further, the development of therapeutic antibodies requires not only technologies that allow the acquisition of antibodies, but also high technological capabilities, including their modifications. In addition to the development of mAb technology, we are committed to the development of antibody engineering technologies such as humanization of antibodies, affinity maturation, and enhancement of the antibody-dependent cellular cytotoxicity (ADCC).

Development of Therapeutic Antibodies

The MBL group develops candidates for therapeutic antibodies targeting cancers, infectious diseases, inflammatory diseases, etc. We have successfully isolated several candidate antibodies exhibiting ADCC, anti-tumor effects, and metastasis suppression effects against cancers. Further, the licensing process of one of the original antibodies developed by MBL is currently in progress, and involves pharmaceutical industries worldwide. In addition, we have successfully developed antibody drug candidates against novel target proteins identified using proteomics technology developed by an MBL affiliate, Oncomics Co., Ltd. These antibodies have already been completely humanized, and are being prepared for joint development with pharmaceutical companies. Institute for Antibodies Co., Ltd. has employed phage display technology to isolate many functional antibodies with high specificity for cancers and with anti-tumor effects. We collaborated with clinicians, used SPYMEG cell lines and the phage display technology with blood from infectious patients, and developed fully human antibodies against viruses such as influenza and hepatitis. We successfully isolated antibodies that neutralize infectious viruses; and in some projects, we have started licensing activities for various pharmaceutical companies. We have also developed several antibodies against targets of inflammatory disease, which were originally discovered by university researchers.

Therapeutic Antibody Development Technology

Humanized Antibody Development

Since therapeutic antibodies are destined for use in humans, antibodies derived from other animals can not be used immediately as pharmaceutical products. In particular, mouse-derived antibodies based on the hybridoma method were initially expected to be "magic bullets;" however, they were recognized as foreign substances by the human body. Due to the emergence of the "human anti-mouse antibody" (HAMA), their use has been discontinued. Development of humanized antibodies was one way to address this issue. Medical Research Council Technology (MRCT) in the United Kingdom possesses leading technology to develop humanized antibodies. To strengthen our capability to develop humanized therapeutic antibodies, MBL has introduced MRCT's technology. Currently, we coupled the MRCT's techniques with MBL's original know-how and humanized candidate antibodies in the aforementioned antibody drug project. We were successfully able to humanize all the mAbs that we had previously handled.

Affinity Maturation Technology

After the systemic administration of therapeutic antibodies, their efficacy can only be expected after they reach the affected part. To achieve this, the antibodies are required to exhibit high binding affinity, with a minimum KD value of < 10–9 M. Therefore, even if functional antibodies exhibit high efficacy in vitro, antibodies with low affinity will show considerably lower efficacy on the target in vivo. The MBL group has established affinity maturation technology, which uses phage display to increase the affinity of the candidate antibodies while maintaining their activity. This technology could enhance the affinity by 10 to 100-fold the level of the original antibody.

ADCC Enhancement Technology

AThe known anti-tumor effects of therapeutic antibodies include the antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and neutralizing activity. Of these, ADCC is considered particularly important; and MBL has discovered that by substituting amino acid residues at particular positions in the constant region of the antibody, the ADCC levels can be increased to 10- to 100-fold of the corresponding levels achieved by wild-type antibodies. We are conducting ongoing research with an aim to further improve the ADCC levels.