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"Welcome to OBGYN World!" A novel recruitment event for medical students organized by the Japan Society of Obstetrics and Gynecology. Since 2012, the number of doctors in Japan who specialize in obstetrics and gynecology has shown a decreasing trend. To increase the number of doctors majoring in obstetrics and gynecology, the Japanese Trainees in Obstetrics and Gynecology subcommittee developed a new recruitment event called Welcome to OBGYN World! (WOW!); the aim of this event was to focus on lower grades of medical students. The present report describes the content of WOW! and the results of a post-event questionnaire administered to participating students and tutors. WOW! was held online in order to avoid the risk of Coronavirus Disease 2019 infection for participants. Sixty of the 82 medical schools nationwide (73.2%) participated in this event. Overall, there were 285 participating students, ranging from first to fourth grade in medical school, and 106 tutors were involved to teach material at the event. In the post-event questionnaire survey, 97.6% (248/254) and 100% of the participants stated they now had a high degree of interest in obstetrics and gynecology and found the specialty attractive, respectively. Furthermore, 93.6% (90/94) of the tutors stated that WOW! had helped recruitment activities in their universities. Based on this outcome, members of the Japanese Trainees of Obstetrics and Gynecology subcommittee will now try to increase the number of doctors specializing in obstetrics and gynecology by holding WOW! annually.

Serous carcinoma (SC) is an aggressive histologic type of endometrial carcinoma (EMC) with a poor prognosis. The development of novel therapeutics for SC is an important issue. PIM1 is a serine/threonine kinase involved in various cellular functions, such as cell cycle progression, apoptosis, and transcriptional activation via the phosphorylation of many target proteins, including MYC. PIM1 is overexpressed in several cancers and has been associated with the treatment-resistance. We investigated the expression and function of PIM1 in EMC, particularly SC. Immunohistochemical analysis in 133 EMC cases [103 endometrioid carcinomas (EC) and 30 SC] revealed the significantly stronger expression of PIM1 in SC than in EC and significantly shorter survival of patients with the overexpression of PIM1 in all EMC cases, as well as in only SC cases. A multivariate analysis identified the overexpression of PIM1 as an independent prognostic factor. The knockdown of PIM1 by siRNA in the SC cell line, ARK1, decreased the expression of phosphorylated MYC and reduced proliferation, migration, and invasion. The PIM1 inhibitor, SGI-1776, reduced cell viability in SC cell lines (ARK1, ARK2, and SPAC1L) with IC50 between 1 and 5 µM. SGI-1776 also reduced the migration and invasion of ARK1 cells. Moreover, the oral administration of SGI-1776 significantly suppressed subcutaneous ARK1 xenograft tumor growth in nude mice without impairing health. These results indicate that PIM1 is involved in the acquisition of aggressiveness and suggest the potential of PIM1 as a novel therapeutic target and SGI-1776 as a therapeutic agent for SC.

Background: Although chimeric antigen receptor (CAR)-T therapies have achieved remarkable success in the treatment of hematologic malignancies, the outcome for patients with solid tumors remains poor. There are several reasons behind this, including exhaustion of CAR-T cell, poor homing and penetration in the tumor, and the lack of persistence in the immunosuppressive tumor microenvironment. To solve these problems, we have developed HER2-CAR-T cells (BP2301) using the piggyBac (PB) transposon-based gene transfer system. Methods and Results: Second generation HER2-CAR construct plus PB transposase were introduced into autologous peripheral blood mononuclear cells (PBMC) by electroporation. These cells were activated with UV-inactivated genetically-engineered antigen presenting autologous PBMC (AP cells) expressing HER2, CD80, and 4-1BBL, and propagated for 14 days to obtain the final product (BP2301). BP2301 exhibited dominant fraction of less exhausted stem cell memory-like T cells (Tscm), which could be associated with antitumor efficacy. BP2301 showed robust in vitro killing activity against HER2+ tumor cells even after multiple rounds of cancer cell challenge, suggesting the long-term functionality without immune-exhaustion. In a xenograft murine model of rhabdomyosarcoma cell line (SJCRh30), a single intravenous administration of BP2301 (5 × 106 CAR-positive cells) eradicated the tumor, and mice treated with BP2301 rejected the second tumor establishment owing to the in vivo expansion of BP2301. Conclusion: BP2301 has demonstrated potent anti-tumor activity in vitro and in vivo. We have established a GMP manufacturing process for BP2301, completed non-clinical safety and efficacy studies, and plan to launch an investigator-initiated phase 1 clinical trial to evaluate the safety and efficacy of BP2301 in HER2-expressing sarcoma and gynecologic malignancies in the second quarter of 2022. Citation Format: Koichiro Shioya, Tomio Matsumura, Yuta Ohira, Naomi Komatsuzaki, Manaka Shinagawa, Miyuki Tanaka, Shigeki Yagyu, Yozo Nakazawa, Lilin Zhang. Development of piggyBac transposon-mediated HER2-CAR-T cells for the treatment of solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5570.