Newsletter Volume 39, Number 2, 2024
Introduction
It is the season of cherry blossoms, and in Tokyo, the blooming of the blossoms seems to coincide with the entrance ceremony for the new school year. The combination of sakura mochi and sencha (green tea) is also very special. But, can you eat the sakura leaves that wrap the sakura mochi? Some of you may have wondered whether you can eat the leaves or not, but I guess some of you have never eaten the leaves. I used to, but I had a problem that the leaves of my favorite “Domyoji Sakura Mochi” were hard to peel off. One day, it became too much of a hassle, and when I finally tried it, I found that the bitter taste of the leaves combined with the saltiness of the sakura-mochi made it even more delicious.
Cherry blossoms have become a symbol of Japan-U.S. exchange, as represented by the rows of cherry trees along the Potomac River, and this year’s joint Japan-U.S. annual meeting will be held in Hawaii in September and is expected to be very exciting. On the other hand, there may be some who are attracted by the attraction of the venue, but are not sure if they will be able to make it work with their busy work schedule. However, meeting with researchers who are different from the usual will be an opportunity to deepen the interest of your research. When in doubt, go!
Antibody Drug Conjugate (ADC) Pharmacokinetic Studies
Part 4: Imaging of ADCs -Exploring the Behavior of ADCs in Tumor Tissue
Pharmacokinetic Research Laboratories, Daiichi Sankyo Company, Limited
Yoko Nagai, Seiya Ogata, Yoko Urasaki
Hello! Since the last issue, we have been reporting on “Introduction to Pharmacokinetic Studies of Antibody Drug Conjugates (ADCs)”. In this fourth issue, I would like to tell you about imaging of ADCs.
The basic concept of ADCs in oncology is to reduce the exposure to normal tissues and to expand the therapeutic range by efficiently delivering highly active drugs to tumors using the high target selectivity of antibodies (see Part 1 ). Trastuzumab delxtecan (T-DXd) is an ADC consisting of an anti-human epidermal growth factor receptor type 2 (HER2) antibody and topoisomerase I inhibitor DXd. The main mechanisms of action are as follows. (1) T-DXd binds to HER2 expressed on cancer cell membranes and internalizes into lysosomes (2) DXd is released by proteases in lysosomes (3) DXd enters the nucleus and induces apoptosis of cancer cells by topoisomerase I inhibition. As mentioned in the second issue of this report, after T-DXd was administered to mice transplanted with HER2-positive tumors, we measured plasma T-DXd concentrations, total antibody concentrations, and DXd concentrations in tumors to confirm fluctuations in plasma ADC concentrations and the presence of DXd in tumor tissue and its transition (changes). … ( To be continued at NL website / members only )