Abstract 43: Application of MiniPDX® in clinical indication identification and anti-tumor drug development

Abstract

Abstract MiniPDX® represents a novel in vivo drug sensitivity test with fast turnaround (7-10 days), using either fresh patient tumor samples or tissues from established PDX models. We systematically evaluated and compared the response rates of MiniPDX® assays and PDX assays pair-wise in 26 PDX models across 3 types of cancers to 12 clinically relevant regimens for chemical and targeting drugs. The results showed a high correlation between drug responses of the two assays, with sensitivity and specificity of 80% and 93%, respectively. More studies of different tumor types showed that MiniPDX drug sensitivity test results were consistent with clinical responses in most patients, which indicated that MiniPDX® models have great potential in guiding personalized cancer therapy. LIDE has completed over 3,000 MiniPDX® tests for clinical precision medicine, covering more than 50 indications. MiniPDX® was used to rank clinically approved drugs or drug regimens to guide the selection of the best individualized treatment strategy. At the same time, screening other compounds facilitates selection of the best drug candidates for further R&D. Importantly, performing MiniPDX® Mouse Trial using fresh tumor samples generated from clinic is beneficial for determination of potential clinical indications. Only thousands of fresh cells leftover from MiniPDX® preparation are sufficient to get genomic and transcription data by OncoVee™ K-cell technology. The combination of MiniPDX® assay and omics data would be very useful for determination of potential bio-markers in order to distinguish responders and non-responders in population with certain indication(s) and leveraged for patient stratification and selection criteria in clinical trial design. Currently, we are developing a new version of MiniPDX® assay for immunotherapy (IO-FIVE, Immuno-Oncology Fast In Vivo Efficacy test) by using fresh patient cancer cells with autologous immune cells to maximally mimic human tumor microenvironment before seeding in immune-deficient mice. Total cell viability and cell phenotyping are tracked before and after drug treatment to evaluate its in vivo efficacy within two weeks. More than 60 samples have been tested and the IO-FIVE functional assay can effectively distinguish the non-responder from responders for immunotherapeutic drugs. Several Investigator Initiated Trials (II-T) are on-going to further validate the correlation of IO-FIVE result to clinic endpoint. Citation Format: Yuan Long, Bin Xie, Hongkui Chen, Shizhu Zhao, Le Li, Song Xi, Danyi Wen. Application of MiniPDX® in clinical indication identification and anti-tumor drug development [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 43.