Abstract 61: Establishment of translational luciferase-based cancer models to evaluate antitumoral therapies

Abstract There is an increased need for translational cancer models in research that can serve as more clinically relevant platforms to better study how cancer develops, the formation of metastases, and for the evaluation of the efficacy of new antitumoral therapies. Orthotopic cancer models represent a valuable opportunity to better understand how cancer cells behave and produce tumors in their primary organs, as well as how the local microenvironment can affect the tumor development. However, studying a growing tumor inside of an animal’s body carries several challenges, like the difficulty to accurately detect the tumor’s presence or changes in size since its location is not always easily accessible. To address this situation, we developed luciferase-based cancer cell lines that can produce bioluminescence (BL) and when inoculated orthotopically, they produce solid tumors that can be detected in live animals, allowing for a more accurate model to evaluate antitumoral therapies. We stably transfected the triple negative breast cancer (TNBC) cell line from human origin HCC1937, and the murine cell line 4T1, as well as the murine lung cancer cell line TC-1 with a luciferase expressing plasmid. After transfection, the luciferase activity was tested in vitro and once confirmed these luciferase-expressing cell lines were inoculated orthotopically into synergic animals. We successfully established orthotopic BL tumors that could be detected by bioluminescence imaging (BLI), as well as the detection of distal metastases by this method. The signal from the tumors in vivo correlated with the signal detected from the ex vivo organs, confirming the high accuracy and sensitivity of the use of BL as a detection method for cancer models. Interestingly, we confirmed a change in phenotype after the plasmid internalization in the cell line HCC1937/luc2. This cell line modified its response to an oncolytic adenovirus virotherapy, downregulating its antiviral response and becoming more sensitive to be infected and killed by these viruses. This highlights the importance of confirming the desired phenotype of a cell line remains unaltered after a genetic modification, as in our case, a plasmid insertion. In our study, we offer clinically relevant bioluminescent orthotopic cancer models that can be used to accurately evaluate the efficacy of antitumoral therapies by the quantification of BL signal coming from live animals. This method facilitates the monitoring of the tumoral growth and the appearance of metastases, with the advantage of allowing for multiple readings over time on live animals to assess the efficacy of antitumoral therapies. Citation Format: Martin R. Ramos-Gonzalez, Nagabhishek S. Natesh, Satyanarayana Rachagani, James Amos-Landgraft, Haval Shirwan, Esma S. Yolcu, Jorge G. Gomez-Gutierrez. Establishment of translational luciferase-based cancer models to evaluate antitumoral therapies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 61.