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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

Item Type:Article
Title: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
Creators Name:Westermann, J. and Floercken, A. and Willimsky, G. and van Lessen, A. and Kopp, J. and Takvorian, A. and Joehrens, K. and Lukowsky, A. and Schoenemann, C. and Sawitzki, B. and Pohla, H. and Frank, R. and Doerken, B. and Schendel, D.J. and Blankenstein, T. and Pezzutto, A.
Abstract: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
Source:Gene Therapy
Publisher:Nature Publishing Group (U.K.)
Page Range:354-363
Date:April 2011
Official Publication:https://doi.org/10.1038/gt.2010.143
PubMed:View item in PubMed

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