PACM-09 NEOANTIGEN PREDICTION AND REACTIVITY OF CEREBROSPINAL FLUID-HUMAN DERIVED TUMOR REACTIVE T CELLS (CSF-TRT CELLS) IN LEPTOMENINGEAL DISEASE (LMD) FROM SOLID TUMORS
Yolanda PinaAbstract
Background
Leptomeningeal disease (LMD) is a devastating complication of metastases. Adoptive cell therapy (ACT) using tumor-infiltrating lymphocytes (TILs) showed complete responses in patients with metastatic melanoma and other solid tumors. To obtain CSF-TRT cells as a source of T cells for ACT, we aim 1) to identify the expansion method that allows higher expansion of tumor reactive TIL; 2) to enrich tumor neoantigen reactive TILs and determine their in-vivo and ex-vivo functional capabilities.
Methods
Cells were isolated from 64 CSF collections from melanoma (M-LMD), 9 CSF from breast cancer (B-LMD), and 9 CSF from lung adenocarcinoma (L-LMD) from patients with LMD. Cells were plated following established TIL culture protocols (high-dose IL-2). Reactivity was assessed with HLA-matched. WES/RNAseq completed in CSF-derived-T-cells and pair-matched extracranial tumors to identify neoantigens using computational algorithms.
Results
After culture in IL-2, 53.4% samples showed increased yield with average 165.29-fold expansion. Cultures produced 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. T-cells expanded from CSF samples from L-LMD and B-LMD had less successful results. L-LMD had a success expansion rate of 11.1% with IL-2 only, 83.3% with T-Activator, 50% CD127 T Activator, and 50% T-Expander. B-LMD had success rate of 22.2% with IL-2 only, 0% with OKT3, 83.3% with T-Activator, 50% with CD137 T-Activator, and 85.7% with T-Expander. Preliminary studies demonstrated CSF TIL reactivity against tumor reactive neoantigens. Ongoing studies will confirm results.
Conclusion
Results demonstrate successful expansion of T cells ex vivo from CSF in M-LMD, raising the potential to use CSF-derived T-cells as therapeutic strategy for LMD. There was a variable success rate with expansion of T cells from CSF from B-LMD and L-LMD and supplementary studies are needed.