Recombinant GM-CSF plus autologous tumor cells as a vaccine for patients with mesothelioma

Abstract

Treatments evaluated for malignant mesothelioma (MM), including chemotherapy, radiotherapy and surgery are of limited efficacy. Immunotherapy has shown some promise in MM but optimal vaccination conditions are yet to be defined. Autologous tumour vaccines have the advantage of containing both 'self'- and 'neo'-tumor antigens but they are not commonly used in any cancer, and never in MM. We therefore evaluated the effect of an autologous MM tumor cell lysate, given s.c. with recombinant granulocyte-macrophage colony stimulating factor (GM-CSF), on anti-tumor immunity in patients with MM. An autologous tumor lysate vaccine was manufactured from surgically resected tumor and administered subcutaneously together with GM-CSF. Induction of tumor specific cellular immunity was assessed by delayed type hypersensitivy (DTH) skin testing using autologous tumor tissue and of humoral immune responses to shared MM antigens by western blotting of patients' sera against a panel of allogeneic human MM cell lines. CT scanning was used to evaluate tumor progression. Twenty-two patients were enrolled onto the trial. Of these five developed positive delayed type hypersensitivity skin tests and five showed evidence of altered antibody specificities by western blotting. A total of seven patients developed at least one type of anti-MM immune response. On an intention-to-treat basis the median survival of all patients was 11.5 months, and the 1- and 2-year survival rates were 50% and 27%, respectively. Complete or partial CT responses were not seen, however seven patients had stable disease for the duration of the trial. Vaccination was safe with no severe adverse reactions. Vaccination with autologous MM tumor cell lysate with GM-CSF induced tumor specific immunity in 32% of patients, was safe and was associated with stable disease but no major tumour regressions.