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New aspects of immunotherapy of leptomeningeal metastasis
U Herrlinger1, M Weller, M Schabet
1Department of Neurology, University of Tuebingen, Germany.
Immunotherapeutic approaches to leptomeningeal metastasis (LM) include the intrathecal application of cytokines such as interleukin-2 (IL-2) and interferon-alpha (IFN-alpha), and lymphokine-activated killer cells (LAK cells). Results in a rodent model of leptomeningeal gliomatosis with intrathecal IL-2 application are discouraging, but some clinical improvement and clearance of neoplastic cells from CSF have been seen in patients with LM from melanoma treated with intrathecal IL-2 alone, and in patients with LM from primary brain tumors and squamous cell carcinoma of the tongue treated with intrathecal LAK cells and IL-2. The neurotoxicity of this therapy, mainly increased intracranial pressure, has been considerable but generally manageable. However, IFN-alpha caused severe neurotoxicity in form of an only partly reversible progressive vegetative state in the majority of patients. Considering the small number of patients treated with IL-2 and LAK cells, its value for the treatment of LM could only be stated by further investigation. In future, the application of recently discovered cytokines such as Fas-ligand, the continuous paracrine cytokine release by genetically modified cells, or vaccination strategies using genetically modified tumor cells might offer new immunotherapeutic approaches in LM.
Immunotherapeutic approaches to leptomeningeal metastasis (LM) include the intrathecal application of cytokines such as interleukin-2 (IL-2) and interferon-alpha (IFN-alpha), and lymphokine-activated killer cells (LAK cells). Results in a rodent model of leptomeningeal gliomatosis with intrathecal IL-2 application are discouraging, but some clinical improvement and clearance of neoplastic cells from CSF have been seen in patients with LM from melanoma treated with intrathecal IL-2 alone, and in patients with LM from primary brain tumors and squamous cell carcinoma of the tongue treated with intrathecal LAK cells and IL-2. The neurotoxicity of this therapy, mainly increased intracranial pressure, has been considerable but generally manageable. However, IFN-alpha caused severe neurotoxicity in form of an only partly reversible progressive vegetative state in the majority of patients. Considering the small number of patients treated with IL-2 and LAK cells, its value for the treatment of LM could only be stated by further investigation. In future, the application of recently discovered cytokines such as Fas-ligand, the continuous paracrine cytokine release by genetically modified cells, or vaccination strategies using genetically modified tumor cells might offer new immunotherapeutic approaches in LM.