TMOD-02. IN VITRO & IN VIVO CULTURE OF PATIENT DERIVED (PD) CSF-CTCS IN LEPTOMENINGEAL DISEASE (LMD) FROM MELANOMA TO IDENTIFY NOVEL TREATMENT STRATEGIES

Abstract

Abstract BACKGROUND Approx. 5% of melanoma pts develop LMD. There are essentially no models of LMD available for therapeutic development. A significant barrier to the development of effective therapies against LMD has been the inability to culture and expand LMD cells. Here we report our strategies to in vitro & in vivo culturing of CSF-CTCs. As a proof of concept, we assessed response to Ceritinib (Cer), a non-canonical IGF1R inhibitor) in combination with MEK inhibitor. METHODS We collected CSF from 11 patients (pts) from various sources (ie: LPs, Ommayas, autopsies). 3 pts CSF were collected at autopsies. PD-CSF-CTCs were expanded in vitro in conditioned media and in vivo using CDX model. scRNAseq analysis was performed to assess expression profiles of PD-CSF-CTCs. RESULTS AND DISCUSSION Of the total 61 PD-CSF-CTCs collected from 11 pts (avg: 4.07 CSF collections/patient), we successfully cultured PD-CSF-CTCs from 3 pts (20%) and were able to grow them in vivo from 2 pts (18%). scRNAseq analysis identified MLANA, IGF1R, SOX9 and ErbB3 were among genes highly expressed in our PD-CSF-CTCs. We evaluated the responses of the combination Cer with MEKi (Tra) in vitro and in vivo and found that these agents produced therapeutic effects to both established melanoma cell lines and our PD-CSF-CTCs. For example, in vivo testing showed a median survival (MS): 18, 35, and 27 days in WM164, WM164R and the PD-CSF-CTCs, respectively, in control groups. Whereas treatment with Cer + Tra produced significantly better MS in all three in vivo models and was not reached in WM164, WM164R (p< 0.001 & p< 0.047, respectively) and 38.5 days in PD-CSF-CTCs (p< 0.032). CONCLUSIONS Though the sample size is small, this is the first report of the successful in vitro & in vivo culture of CSF-CTCs from pts with LMD.