Intrathecal Cytotoxic T-Cell Immunotherapy for Metastatic Leptomeningeal Melanoma

• Published in: Clinical cancer research 2001-03, Vol.7 (3), p.917s-924s
• Main Authors: CLEMONS-MILLER, Annette R, CHATTA, Gurkamal S, HUTCHINS, Laura, ANGTUACO, Edgardo J, RAVAGGI, Antonella, SANTIN, Alessandro D, CANNON, Martin J
• Format: Article
• Language: English
• Subjects: Antigens, Neoplasm; Antineoplastic agents; B-Lymphocytes - metabolism; Biological and medical sciences; CD8-Positive T-Lymphocytes - metabolism; Cytokines - biosynthesis; Dendritic Cells - metabolism; Enzyme-Linked Immunosorbent Assay; Female; Flow Cytometry; gp100 Melanoma Antigen; Humans; Immunotherapy; Immunotherapy, Adoptive; Indium - metabolism; Interferon-gamma - biosynthesis; Interferon-gamma - metabolism; Interleukin-2 - metabolism; Interleukin-4 - metabolism; Interleukin-6 - biosynthesis; MART-1 Antigen; Medical sciences; Melanoma - therapy; Membrane Glycoproteins; Meningeal Neoplasms - therapy; Middle Aged; Monophenol Monooxygenase - chemistry; Neoplasm Proteins - chemistry; Pharmacology. Drug treatments; Proteins; Reverse Transcriptase Polymerase Chain Reaction; T-Lymphocytes, Cytotoxic - metabolism; Time Factors; Tissue Distribution; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha - biosynthesis
• ISSN: 1078-0432; 1557-3265

A 49-year-old patient with primary, recurrent melanoma on the lower extremity developed metastatic leptomeningeal melanoma that did not respond to treatment 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 melanoma-associated antigens tyrosinase (145–156), Melan-A/MART-1 (26–35), and gp100/Pmel 17 (209–217). The CTLs exhibited up to 74% specific lysis against peptide-pulsed autologous EBV-transformed B cells, with Melan-A-specific CTLs yielding the greatest lytic activity. CD8 + CTLs possessed a type 1 cytokine profile, expressing tumor necrosis factor α and IFN γ but not IL-4. Infusions of CTLs were supported with systemic low-dose IL-2 administration. 111 In labeling and computerized gamma imaging were used to monitor the distribution of CTLs up to 48 h after infusion. Intra-arterial delivery via the right carotid artery was followed by redistribution of the CTLs to the lungs, liver, and spleen within 16 h. In contrast, delivery via an indwelling 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 α, IFN- γ , and IL-6 in the cerebrospinal fluid were observed within 4 h of CTL infusion. There was no evidence of tumor progression throughout the treatment period, and clinically the patient showed some resolution of neurological symptoms.