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Long-Term Survival In Metastatic Melanoma Patients With Leptomeningeal Disease Treated With Intrathecal Interleukin-2, Isabella C. Glitza Oliva

Dissertations & Theses (Open Access)

BACKGROUND: Metastatic melanoma patients with leptomeningeal disease (LMD) have an extremely poor prognosis and a paucity of effective treatment options. We assessed the safety and efficacy of intrathecal interleukin-2 (IT IL-2) in metastatic melanoma patients with LMD.

METHODS: We reviewed the outcomes of 43 consecutive metastatic melanoma patients with LMD who were treated with IT IL-2 from 2006 to 2014 in a Compassionate Investigational New Drug Study. All patients had evidence of LMD based on cerebrospinal fluid (CSF) cytology, radiology, and/or surgical pathology. IL-2 at a dose of 1.2 mIU was administered intrathecally via Ommaya reservoir up to 5 times …

Mechanistic And Functional Characterization Of B And T Lymphocyte Attenuator (Btla) In Cd8 Tumor Infiltrating Lymphocytes, Krit Ritthipichai

Dissertations & Theses (Open Access)

This dissertation project focused on understanding the functional role of BTLA on CD8⁺ Tumor Infiltrating Lymphocytes (TIL) from metastatic melanoma patients. Clinical trials of adoptive T-cell therapy (ACT) using autologous ex vivo expanded TIL have demonstrated the great potential of this immunotherapy with an overall clinical response rate 40-50% for stage IV metastatic melanoma patients. We have investigated a number of biomarkers in both the infused TIL and the tumor microenvironment for their association with clinical response. Surprisingly, a subset of CD8⁺ TIL expressing the co-inhibitory molecule BTLA (B-and-T lymphocyte attenuator) was highly associated with clinical response, while …