Research & Development
Therapeutic Antibody Projects
We have been devoting our effort to develop candidates of therapeutic antibodies targeting cancer, infections, and inflammatory diseases.
We have already succeeded in developing an antibody against a target molecule, one of EGFR ligands, which functions as an autocrine growth factor for cancers and plays a role in the development of cancer-growing stroma. It has a stronger inhibitory activity on EGFR phosphorylation signals than existing neutralizing antibodies and cetuximab, an EGFR-blocking antibody. This therapeutic antibody candidate showed very useful outcome in that it exhibited strong therapeutic effects to cancers with KRAS mutation that are resistant to cetuximab. We have applied for a patent on this antibody, and have licensed-out to pharmaceutical companies in Japan and overseas.
In addition, we have successfully developed a therapeutic antibody candidate for a target protein found by Oncomics Co., Ltd., a company affiliated with MBL. We have completed humanization of this antibody as well as patent application, and are preparing to perform joint research with pharmaceutical companies. For antibody candidates for neutralizing viruses, we have engaged in joint studies with domestic and foreign institutes. In addition, we have isolated many therapeutic antibody candidates with interesting activities, for which we are currently preparing to obtain intellectual property rights.
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.