Abstract 3716: Conditional reprogramming technology for Next Generation Living Biobanks (NGLB)

Abstract

Abstract As one of the next generation biobanks, living biobanks (iPSC, organoids, CRC, PDX, etc.) and related functional analyses are rapidly growing in basic research, clinics, and industry (especially immune-oncology and targeting therapies) as well. Most recently NCI launched PDMR (patient-derived model repository) using PDX, CRC and organoid cultures, NCI/ATCC/Broad/Sanger launched HCMI (Human Cancer Models Initiative) using Organoids and CRC cultures. In this study, we established a conditional reprogramming (CR) protocol which allows to generate cell cultures from cryopreserve fresh tissue specimens from surgery, core biopsies, needle biopsies, and brushed cells.It has been extremely difficult to generate primary cultures from tumor specimens, it has not been possible to expand and indefinitely propagate cells derived from adult tissues while retaining lineage-commitment, normal growth control and differentiation potential. The CR method rapidly expands both normal and malignant epithelial cells from diverse anatomic sites and mammalian species and does not require transfection with exogenous viral or cellular genes. Establishment of cell cultures from both normal and tumor tissue (many types) is highly efficient. The robust nature of the technique is exemplified by the ability to produce 2 x 106cells in 5 days from a core biopsy of breast tumor. Normal cultures retain a normal karyotype and differentiation potential and cell lines derived from tumors retain their tumorigenic phenotype. We were also able to generate their corresponding fibroblast cultures from the same specimens. These fibroblasts can be immortalized by exogenously expressed hTERT. This approach allows to establish in vitro "epithelial-stroma interactions" to study normal cell differentiation and tumor microenvironment. The ability to produce inexhaustible cell populations from small biopsies and cryopreserved specimens has the potential to transform biobanking repositories (termed as NGLB - next generation living biobanks) and current pathology practice by enabling genetic, biochemical, metabolomic, proteomic, and biological assays, including chemosensitivity testing as a functional diagnostics tool (or a living biomarker) for precision cancer medicine. CR cells can be also an inexhaustible resource to generate CR cells derived iPSC, organoids, and xenografts (CDXs). Citation Format: Xuefeng Liu. Conditional reprogramming technology for Next Generation Living Biobanks (NGLB) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3716.