Abstract 1449: The valuable experimental model system “Cancer Xenopatient” established in NOG mice
Authors: Chijiwa Tsuyoshi , Kawai Kenji , Noguchi Akira , Sato Hidemitsu , Hayashi Akimune , Cho Haruhiko , Shiozawa Manabu , Kishida Takeshi , Morinaga Soichiro , Yokose Tomoyuki , Katayama Makoto , Takenaka Nobuo , Suemizu Hiroshi , Yamada Roppei , Nakamura Yoshiyasu , Takano Yasuo , Imai Kohzoh , Miyagi Yohei , Nakamura Masato 
Published: August 2015

Viable and stable human cancer materials combined with adequate clinical information are required for advance in cancer research and patient care. Conventional in vitro cancer cell lines are commonly available without enough information on the patient including disease phenotypes and drug-sensitivity. Mice bearing Patient-derived xenografts (PDXs) with clinical information (so-called “cancer xenopatients”) could be essential and useful systems to accelerate cancer medicine. In this study, we investigated the establishment efficiency of PDX using NOG mice with clinical factors of xeno-transplantaion. The NOG mouse, the NOD/Shi-scid/IL-2Rγnull (NOG) mice derived from the NOD/SCID mouse with a common gamma chain, has multifunctional defects in natural killer cell activity, macrophage function, complement activity, and dendritic cell function in addition to lacking functional T and B lymphocytes. NOG mice were reported to be the best appropriate immunodeficient host animal for direct xenografting of fresh tumor tissue. We also discuss herein its contribution for not only reliable preclinical studies of new anticancer drugs but also personalized anti-cancer therapies. Sixty-one PDX lines were established from 116 surgically removed tumor tissues inoculated into NOG mice's subcutaneous (53%). PDX lines were established from various types of epithelial tumors and also from sarcomas including gastrointestinal stromal tumor and Ewing/PNET sarcoma. The metastatic tumors yielded PDX lines effectively (65%) than the primary tumors (27%, p&lt;0.001). The group engrafted into NOG mice after 2 days or later from the surgical removal showed a higher establishment rate (61%) than that of the group engrafted at the day of surgery or the next day (51%), however non-significant (p = 0.49). Our PDX models were preserved well not only in morphological characteristics but also in gene expression and alteration patterns. In 8 cases (7%), the transplantable xenografts for several generations were composed of monotonous large non-epithelial cell growth of human origin, revealed to be the Epstein-Barr virus (EBV) infection associated lymphoprolipherative lesions prospected by chromogenic in situ hybridization for EBV-encoded RNA. We revealed efficient establishment rates both for primary tumors and metastatic tumors. PDXs linked with clinical information will contribute to reliable preclinical studies for new anticancer drugs. The fast and efficient establishment of individual PDXs may also contribute to future personalized anti-cancer therapies.

Citation Format: Tsuyoshi Chijiwa, Kenji Kawai, Akira Noguchi, Hidemitsu Sato, Akimune Hayashi, Haruhiko Cho, Manabu Shiozawa, Takeshi Kishida, Soichiro Morinaga, Tomoyuki Yokose, Makoto Katayama, Nobuo Takenaka, Hiroshi Suemizu, Roppei Yamada, Yoshiyasu Nakamura, Yasuo Takano, Kohzoh Imai, Yohei Miyagi, Masato Nakamura. The valuable experimental model system “Cancer Xenopatient” established in NOG mice. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1449. doi:10.1158/1538-7445.AM2015-1449