Publikationen

Gene Therapy 18 (4): 354-363 (2011-04)

Westermann J.; Floercken A.; Willimsky G.; van Lessen A.; Kopp J.; Takvorian A.; Joehrens K.; Lukowsky A.; Schoenemann C.; Sawitzki B.; Pohla H.; Frank R.; Doerken B.; Schendel D.J.; Blankenstein T.; Pezzutto A.

Allogeneic gene-modified tumor cells (RCC-26/IL-7/CD80) as a vaccine in patients with metastatic renal cell cancer: a clinical phase-I study

Description:
Despite novel targeted agents, prognosis of metastatic renal cell cancer (RCC) remains poor, and experimental therapeutic strategies are warranted. Transfection of tumor cells with co-stimulatory molecules and/or cytokines is able to increase immunogenicity. Therefore, in our clinical study, 10 human leukocyte antigen (HLA)-A(*)0201(+) patients with histologically-confirmed progressive metastatic clear cell RCC were immunized repetitively over 22 weeks with 2.5-40 x 10(6) interleukin (IL)-7/CD80 cotransfected allogeneic HLA-A(*)0201(+) tumor cells (RCC26/IL-7/CD80). Endpoints of the study were feasibility, safety, immunological and clinical responses. Vaccination was feasible and safe. In all, 50% of the patients showed stable disease throughout the study; the median time to progression was 18 weeks. However, vaccination with allogeneic RCC26/IL-7/CD80 tumor cells was not able to induce TH1-polarized immune responses. A TH2 cytokine profile with increasing amounts of antigen-specific IL-10 secretion was observed in most of the responding patients. Interferon-γ secretion by patient lymphocytes upon antigen-specific and non-specific stimulation was substantially impaired, both before and during vaccination, as compared with healthy controls. This is possibly due to profound tumor-induced immunosuppression, which may prevent induction of antitumor immune responses by the gene-modified vaccine. Vaccination in minimal residual disease with concurrent depletion of regulatory cells might be one strategy to overcome this limitation.

Keywords: Allogeneic Vaccine, Renal Cell Carcinoma, Gene Transfer, Tumor Vaccination

Type: Article

PubMed: 21068778
Official URL: https://doi.org/10.1038/gt.2010.143
MDC Repository: https://edoc.mdc-berlin.de/11271/