title: Regression of human metastatic renal cell carcinoma after vaccination with tumor cell-dendritic cell hybrids.
abstract: Reports of spontaneous regressions of metastases and the demonstration of tumor-reactive cytotoxic T lymphocytes indicate the importance of the host's immune system in controlling the devastating course of metastatic renal cell carcinoma. Recent research indicates that immunization with hybrids of tumor and antigen presenting cells results in protective immunity and rejection of established tumors in various rodent models. Here, we present a hybrid cell vaccination study of 17 patients. Using electrofusion techniques, we generated hybrids of autologous tumor and allogeneic dendritic cells that presented antigens expressed by the tumor in concert with the co-stimulating capabilities of dendritic cells. After vaccination, and with a mean follow-up time of 13 months, four patients completely rejected all metastatic tumor lesions, one presented a 'mixed response', and two had a tumor mass reduction of greater 50%. We also demonstrate induction of HLA-A2-restricted cytotoxic T cells reactive with the Muc1 tumor-associated antigen and recruitment of CD8+ lymphocytes into tumor challenge sites. Our data indicate that hybrid cell vaccination is a safe and effective therapy for renal cell carcinoma and may provide a broadly applicable strategy for other malignancies with unknown antigens.
authors.affiliation: Department of Urology, University of Göttingen, Germany. akugler@gwdg.de
authors.forename: A
authors.initials: A
authors.lastname: Kugler
authors.forename: G
authors.initials: G
authors.lastname: Stuhler
authors.forename: P
authors.initials: P
authors.lastname: Walden
authors.forename: G
authors.initials: G
authors.lastname: Zöller
authors.forename: A
authors.initials: A
authors.lastname: Zobywalski
authors.forename: P
authors.initials: P
authors.lastname: Brossart
authors.forename: U
authors.initials: U
authors.lastname: Trefzer
authors.forename: S
authors.initials: S
authors.lastname: Ullrich
authors.forename: C A
authors.initials: CA
authors.lastname: Müller
authors.forename: V
authors.initials: V
authors.lastname: Becker
authors.forename: A J
authors.initials: AJ
authors.lastname: Gross
authors.forename: B
authors.initials: B
authors.lastname: Hemmerlein
authors.forename: L
authors.initials: L
authors.lastname: Kanz
authors.forename: G A
authors.initials: GA
authors.lastname: Müller
authors.forename: R H
authors.initials: RH
authors.lastname: Ringert
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D019496:Cancer Vaccines / Q000009:adverse effects; D002292:Carcinoma, Renal Cell / Q000276:immunology* / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation; D006801:Humans; D006822:Hybrid Cells / Q000276:immunology* / Q000637:transplantation; D007371:Interferon-gamma / Q000097:blood; D007680:Kidney Neoplasms / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008214:Lymphocytes / Q000276:immunology; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D016019:Survival Analysis; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D019496:Cancer Vaccines; D007371:Interferon-gamma