Installment of Automation and Modernized Culture Methods Updates a Drug-Sensitivity Screening Platform and Paves the Way to Next-Generation of Precision Medicine

作者：Kimihito C. Kawabata, Chao Li, Hideaki Kakinuma, Yoshiharu Takama, Hayato Tsuji, Hironobu Komori, Bo Gong, Yasumasa Kimura, Hideki Tanomura, Atsushi Okamoto, Maiko Morita, Hiroyuki Takamori, Hidehito Fukushima, Kazuaki Yokoyama, Takaaki Konuma, Nobuhiro Ohno, Susumu Goyama, Satoshi Yamazaki, Tetsushi Oka, Gen Kudo, Ari Melnick, Yasuhito Nannya, Seiya Imoto, Satoshi Takahashi · 发表于：Blood · 年份：2024 · DOI：10.1182/blood-2024-199921 · 研究领域：Biosimilars and Bioanalytical Methods、Computational Drug Discovery Methods、Cell Image Analysis Techniques

Since the field of drug discovery has seen a rise in the use of primary tumor specimens (PTS) derived from patients with hematological malignancies as live materials in ex vivo drug treatments in late 2010s, they have discovered many intriguing phenotypes of AML cells that can lead to therapeutic insights of this disease category. However, when we consider the fact that current methods in ex vivo drug screenings are not using the most updated culture and cell processing methodology, it is highly expected that modernization of cell processing and analyzing procedures will enable us to detect phenotypes of PTS at a higher resolution. Herein, we have installed our own updated methods in multimodal categories. Even though the number of primary tumor specimens in the screening cohort is not comparable to the ones in other studies using AML PTS, (24 cases of AML, 3 cases of CML, and 1 case of MPN, while we ongoingly recruit more cells), our approach is characterized by its full-automation both in cell processing and data acquisitions using multicolor flow cytometry, as well as updated ex vivo culture methods after optimization using different culture media. We harvested cells for flow cytometry as of day 0, 3, and 6. In a monotherapy section, 24 compounds (6 conventional chemotherapy drugs, 10 epigenetic inhibitors, 4 kinase inhibitors including a FLT3 inhibitor, 3 signal transduction inhibitors, and Venetoclax) were included, while 3 different combination therapies (IDR+ AraC, Ven...