title: Allogeneic partially HLA-matched dendritic cells pulsed with autologous tumor cell lysate as a vaccine in metastatic renal cell cancer: a clinical phase I/II study.
abstract: Multi-kinase inhibitors have been established for the treatment of advanced renal cell cancer, but long-term results are still disappointing and immunotherapeutic approaches remain an interesting experimental option particularly in patients with a low tumor burden. DC are crucial for antigen-specific MHC-restricted T cell immunity. Furthermore, allogeneic HLA-molecules pose a strong immunogenic signal and may help to induce tumor-specific T cell responses. In this phase I/II trial, 7 patients with histologically confirmed progressive metastatic RCC were immunized repetitively with 1 × 10 (7) allogeneic partially HLA-matched DC pulsed with autologous tumor lysate following a schedule of 8 vaccinations over 20 weeks. Patients also received 3 Mio IE IL-2 s.c. once daily starting in week 4. Primary endpoints of the study were feasibility and safety. Secondary endpoints were immunological and clinical responses. Vaccination was feasible and safe with no severe toxicity being observed. No objective response could be documented. However, while all patients had documented progress at study entry, 29% of the patients showed SD throughout the study with a mean TTP of 24.6 weeks (range 5 to 96 weeks). In 3/7 patients, TH1-polarized immune responses against RCC-associated antigens were observed. In one patient showing a minimal clinical response and a TTP of 96 weeks, clonally proliferated T cells against yet undefined antigens were induced by the vaccine. Vaccination with tumor antigen loaded DC remains an interesting experimental approach, but should rather be applied in the situation of minimal residual disease after systemic therapy. Additional depletion of regulatory cells might be a promising strategy.
authors: Department of Hematology; Oncology, and Tumor Immunology; Charité University Medicine Berlin; Campus Virchow- Klinikum; Berlin, Germany; Department of Hematology; Oncology, and Tumor Immunology; Charité University Medicine Berlin; Campus Benjamin Franklin; Berlin, Germany.
authors: Anne
authors: A
authors: Flörcken
authors: Joachim
authors: J
authors: Kopp
authors: Antje
authors: A
authors: van Lessen
authors: Kamran
authors: K
authors: Movassaghi
authors: Anna
authors: A
authors: Takvorian
authors: Korinna
authors: K
authors: Jöhrens
authors: Markus
authors: M
authors: Möbs
authors: Constanze
authors: C
authors: Schönemann
authors: Birgit
authors: B
authors: Sawitzki
authors: Karl
authors: K
authors: Egerer
authors: Bernd
authors: B
authors: Dörken
authors: Antonio
authors: A
authors: Pezzutto
authors: Jörg
authors: J
authors: Westermann
mesh_terms: D000328:Adult; D000368:Aged; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000009:adverse effects; D002292:Carcinoma, Renal Cell / Q000628:therapy*; D002457:Cell Extracts; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D004705:Endocytosis; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000009:adverse effects / Q000379:methods*; D008297:Male; D008875:Middle Aged; D010750:Phosphoproteins / Q000276:immunology*; D016896:Treatment Outcome
chemical_list: D019496:Cancer Vaccines; D002457:Cell Extracts; C574674:La protein, human; D010750:Phosphoproteins
keywords: T cell response; dendritic cells; immune response; renal cell cancer; tumor vaccination