IMMU-28. Cerebrospinal Fluid-Derived Tumor Reactive T cells (CSF-TRT cells) As Potential Adoptive Cell Therapy (ACT) for Leptomeningeal Disease (LMD) from Melanoma and Other Solid Tumors

Abstract BACKGROUND Leptomeningeal disease (LMD), a devastating complication of metastatic cancers, has a median survival of weeks to a few months. LMD incidence is highest in melanoma (5-25%), carrying the worst prognosis. Adoptive cell therapy (ACT) using tumor-infiltrating lymphocytes (TILs) has demonstrated complete and durable responses in patients with advanced metastatic melanoma, including regression of brain metastases, and other solid tumors i.e., lung cancer. We are optimizing rapid expansion of CSF-TRT cells as a source of T cells for ACT. We aim to evaluate CSF-TRT cells and determine their tumor reactivity ex-vivo/in-vivo to develop a novel therapeutic approach. METHODS Cells from the CSF from melanoma (M-LMD) patients (n=26; via lumbar puncture/Ommaya) were plated following established TIL culture protocols (high-dose IL-2): 1) OKT3, 2) anti-4-1BB-agonist, 3) IL-7+IL-15+IL-21, 4) anti-CD3/CD28-T-activator, 5) anti-CD3/CD28/CD137-T-activator, 6) anti-CD3/CD28-T-expander. After 4-6 weeks, reactivity was assessed with HLA-matched or autologous tumor cells. We are investigating tumor-based genomic correlates with whole exome sequencing (WES) by interrogating tumor samples initially collected from extracranial disease, and response to therapy in vivo in our LMD mouse model. Similar studies are underway for other solid tumors including lung cancer. RESULTS After initial culture in IL-2, 53.4% of samples showed increased cell yield with average 165.29-fold expansion. PreREP resulted in 37.6% CD8+ T cells. REP was completed with a 96.8% success rate (mean 589.87-fold expansion). Post-REP flow cytometry revealed expansion of CD4+ T cells. Additional cultures produced similar yields with reduced T cell input requirement and demonstrated the potential to enrich for CD8+ T cells. Out of five samples tested for reactivity to HLA-matched melanoma cell lines, three produced varying levels of IFN-y. Results from WES, in vivo experiments, and testing other solid tumors are ongoing with pending results. CONCLUSION Results demonstrate successful expansion of T cells ex vivo from CSF in M-LMD, raising the potential to use autologous CSF-derived T-cells as therapeutic strategy for patients with LMD.