title: Immunological response and overall survival in a subset of advanced renal cell carcinoma patients from a randomized phase 2/3 study of naptumomab estafenatox plus IFN-α versus IFN-α.
abstract: Naptumomab estafenatox/ABR-217620/ANYARA (Nap) has been evaluated in clinical phase 1 and 2/3 studies. RCC patients in the phase 2/3 trial were randomized 1:1 in an open label study to receive Nap+IFN-α or IFN-α. In this study, we analyzed the UK patients for their immunological response in relation to prolonged overall survival (OS). We found that Nap-specific T cells were reduced after 3 treatment days in patients' peripheral blood. Levels of both Nap-specific CD4+ and CD8+ T cells were significantly higher 8 days after the first treatment. Patients with such pattern of reduction and expansion of Nap-binding T cells also showed increased levels of IL-2 and IFN-γ in plasma 3 hours after the first Nap treatment. In addition, Nap caused an increase of IL-6, IL-10 and TNF-α. The patients in the UK subset showed a tendency of OS benefit after Nap treatment. Most Nap treated patients with long OS had low baseline IL-6 and normal levels of anti-SEA/E-120 antibodies. Furthermore, patients with pronounced Nap induced IL-2 and T cell expansion had long OS. In conclusion, patients with low baseline IL-6 and normal anti-SEA/E-120 may respond well to Nap by T cell activation and expansion paving the way for anti-tumour effects.
authors: Department of Medical Oncology, Institute of Cancer Sciences, The University of Manchester, Manchester, UK.|Department of Medical Microbiology & Immunology, College of Medicine & Health Sciences, United Arab Emirates University, Al Ain, UAE.|Biomedical Research Centre, School of Environment & Life Sciences, University of Salford, Salford, UK.
authors: Eyad
authors: E
authors: Elkord
authors: Department of Medical Oncology, Institute of Cancer Sciences, The University of Manchester, Manchester, UK.
authors: Deborah J
authors: DJ
authors: Burt
authors: Active Biotech AB, Lund, Sweden.
authors: Anette
authors: A
authors: Sundstedt
authors: Active Biotech AB, Lund, Sweden.
authors: Örjan
authors: Ö
authors: Nordle
authors: Active Biotech AB, Lund, Sweden.
authors: Gunnar
authors: G
authors: Hedlund
authors: Department of Medical Oncology, Institute of Cancer Sciences, The University of Manchester, Manchester, UK.
authors: Robert E
authors: RE
authors: Hawkins
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D004768:Enterotoxins / Q000627:therapeutic use*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D018796:Immunoconjugates / Q000627:therapeutic use*; D016898:Interferon-alpha / Q000627:therapeutic use; D015850:Interleukin-6 / Q000097:blood; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000187:drug effects*; D013601:T-Lymphocytes / Q000187:drug effects; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D004768:Enterotoxins; C508600:IL6 protein, human; D018796:Immunoconjugates; D016898:Interferon-alpha; D015850:Interleukin-6; C543500:naptumomab estafenatox