Intrathecal cytotoxic T-cell immunotherapy for metastatic leptomeningeal melanoma

A 49-year-old patient with primary, recurrent melanoma on the lower extremi ty developed metastatic leptomeningeal melanoma that did not respond to tre atment with radiation therapy or intrathecal interleukin 2 (IL-2). Disease was characterized by neurological symptoms, including loss of hearing, loss of short-term memory, and gait disturbance. CD8(+) CTLs were generated in vitro using autologous dendritic cells pulsed with peptides from the melano ma-associated antigens tyrosinase (1.45-156), Melan-A/MART-1 (26-35), and g p100/Pmel 17 (209-217), The CTLs exhibited up to 74 % specific lysis agains t peptide-pulsed autologous EBV-transformed B cells, with Melan-A-specific CTLs yielding the greatest lytic activity. CD8(+) CTLs possessed a type 1 c ytokine profile, expressing tumor necrosis factor or and IFN gamma but not IL-4. Infusions of CTLs were supported with systemic low-dose IL-2 administ ration. In-111 labeling and computerized gamma imaging were used to monitor the distribution of CTLs up to 48 h after infusion. Intra-arterial deliver y via the right carotid artery was followed by redistribution of the CTLs t o the lungs, liver, and spleen within 16 h, m contrast, delivery via an ind welling Ommaya reservoir resulted in prolonged retention of CTLs within the brain for at least 48 h after infusion. Marked but transient elevations in tumor necrosis factor or, IFN-gamma, and IL-6 in the cerebrospinal fluid w ere observed within 4 h of CTL infusion. There was no evidence of tumor pro gression throughout the treatment period, and clinically the patient showed some resolution of neurological symptoms.