Immunological effects of the TGFβ-blocking antibody GC1008 in malignant pleural mesothelioma patients.
We evaluated a neutralizing anti-TGFβ antibody (GC1008) in cancer patients with malignant pleura mesothelioma (MPM). The goal of this study was to assess immunoregulatory effects in relation to clinical safety and clinical response. Patients with progressive MPM and 1-2 prior systemic therapies received GC1008 at 3mg/kg IV over 90 min every 21 d as part of an open-label, two-center Phase II trial. Following TGFβ blockade therapy, clinical safety and patient survival were monitored along with the effects of anti-TGFβ antibodies on serum biomarkers and peripheral blood mononuclear cells (PBMC). Although designed as a larger trial, only 13 patients were enrolled when the manufacturer discontinued further development of the antibody for oncology indications. All participants tolerated therapy. Although partial or complete radiographic responses were not observed, three patients showed stable disease at 3 mo. GC1008 had no effect in the expression of NK, CD4
Published In/Presented At
Stevenson, J. P., Kindler, H. L., Papasavvas, E., Sun, J., Jacobs-Small, M., Hull, J., Schwed, D., Ranganathan, A., Newick, K., Heitjan, D. F., Langer, C. J., McPherson, J. M., Montaner, L. J., & Albelda, S. M. (2013). Immunological effects of the TGFβ-blocking antibody GC1008 in malignant pleural mesothelioma patients. Oncoimmunology, 2(8), e26218. https://doi.org/10.4161/onci.26218
Medicine and Health Sciences
Department of Medicine