Abstract C117: Development of autologous tumor: TIL coculture from patient-derived samples for in vitro preclinical immuno-oncology studies

Abstract

Abstract For over two decades, tumor infiltrating lymphocytes (TILs) have been utilized as an adoptive cell transfer therapy to treat cancer in clinical trials. In combination with added immunotherapy treatments, such as IL-2 or anti-CTLA4, TIL therapy has further improved clinic response rate. Following isolation from a patient’s own tumor specimen, TILs that recognize tumor-specific known or unknown antigens can be expanded. These cells are then infused back into tumor-bearing patients to attack the autologous cancer cell population. Despite progress in clinical research, preclinical and translational models of autologous tumor:TIL coculture have been difficult to establish. Our present study established autologous tumor:TIL coculture methods directly from patient tumor specimens. Models were established from BioDuro’s viably frozen tumor bank, containing more than 100,000 patient biospecimens. Each patient specimen contains a heterogeneous population of cell types, including tumor cells, TILs and TAFs (tumor associated fibroblasts). To establish our patient-derived coculture system, these cell populations were expanded under specific growth conditions to then serve as components of the coculture system. In this study, TILs and monocytes from a cohort of patient tumor specimens were analyzed by FACS to evaluate surface receptor expression. Leukocytes, T cells, monocytes and B cells were marked with CD45, CD3, CD14, CD20, respectively. PD-1 expression levels were also evaluated, with the results showing significant individual variation of expression on cell subpopulations. Established methods were used for the expansion of TILS, supporting either CD4 or CD8 T cell phenotypes. Autologous tumor cells were also expanded, concurrently. Afterward, TILs and tumor cells were cocultured and tumor cell killing was monitored using high content fluorescent image cytometry. We found that autologous patient-matched TILs showed preferential tumor cell killing as compared to coculture with patient-unmatched TILs. This response was observed in a dose-dependent manner. In conclusion, BioDuro’s biobank of viably frozen tumor and TIL patient specimens serves as an expansive and powerful immunooncology resource to establish patient-derived autologous tumor:TIL coculture assays. These assays, along with the ability to readily study larger populations of cancer patients, provide a powerful in vitro platform to test immunooncology drug candidates. Citation Format: Kaede Hinata, Patrice Cuff, Wei Liang, Thomas Broudy. Development of autologous tumor: TIL coculture from patient-derived samples for in vitro preclinical immuno-oncology studies [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr C117. doi:10.1158/1535-7163.TARG-19-C117