
==== Front
Neurooncol Adv
Neurooncol Adv
noa
Neuro-Oncology Advances
2632-2498
Oxford University Press US

10.1093/noajnl/vdae090.133
vdae090.133
Final Category: Translational Science
AcademicSubjects/MED00300
AcademicSubjects/MED00310
TRSC-05 TUMOR REACTIVE T CELLS FROM THE CEREBROSPINAL FLUID IN MELANOMA LEPTOMENINGEAL DISEASE
Pina Yolanda Tampa, Tampa, USA

Carter Michael Moffitt Cancer Center, FL, USA

Hall Maclean Moffitt Cancer Center, FL, USA

Rodriguez Madeline Moffitt Cancer Center, FL, USA

Beatty Matthew Moffitt Cancer Center, FL, USA

Forsyth Peter Moffitt Cancer Center, FL, USA

Pilon-Thomas Shari Moffitt Cancer Center, FL, USA

8 2024
02 8 2024
02 8 2024
6 Suppl 1 2024 SNO/ASCO CNS Metastases Conference i40i40
© The Author(s) 2024. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.
2024
https://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

Abstract

BACKGROUND

Leptomeningeal disease (LMD) is a devastating complication from cancer, with a median survival of 6-8 weeks. The incidence of LMD is highest in melanoma (5-25%) carrying the worst prognosis. Adoptive cell therapy (ACT) using tumor-infiltrating lymphocytes (TILs) showed complete and durable responses in patients with advanced metastatic melanoma. CSF-derived T cell populations in LMD shift to more exhausted phenotypes compared to extracranial and brain metastases. Adoptive T cell transfer can be a novel therapeutic approach to treat melanoma LMD (M-LMD). Our goal is to optimize CSF-derived tumor reactive T cell expansion in M-LMD and assess their anti-tumoral response.

METHODS

Cells from CSF from M-LMD patients (n=6) were plated following established TIL culture protocols to determine optimal expansion conditions i.e.: 1) 6000 IU/mL IL-2, 2) IL-2+OKT3, 3) IL-2+anti-4-1BB agonistic antibody, 4) IL-2+IL-7+IL-15+IL-21, 5) IL-2+anti-CD3/CD28 human dynabeads, & 6) IL-2+anti-CD3/CD28/CD137 human dynabeads. After 4 weeks, T cells were propagated via REP and phenotyped. T cells were co-cultured with HLA-matched melanoma cell lines and IFN-y levels evaluated. TCR beta seq was done at different times point of expansion and peripheral T cells.

RESULTS

After initial culture in IL-2, 61.9% of samples showed increased cell yield with an average 101.68-fold expansion (range 2.35-1054). PreREP T cells were predominantly CD4+ (45.7%). REP was 100% success rate (mean 187.47-fold expansion). Post-REP flow cytometry revealed similar results. M-LMD T cells were highly functional, producing substantial levels of IFN-y in response to HLA-matched cells. Anti-CD3/CD28 produced a larger expansion of T cells with higher levels of IFN-y. TCR beta sequencing results are pending.

CONCLUSIONS

Therapies for LMD patients are desperately needed. Results demonstrate successful expansion of T cells ex vivo from CSF in M-LMD. Results raise potential to use autologous CSF-derived T cells as therapeutic strategy for patients with LMD.
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